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10 pages, 732 KiB

Open AccessCommunication

Antioxidant and Anti-Proliferative Activity of Essential Oil and Main Components from Leaves of Aloysia polystachya Harvested in Central Chile

by Alejandra Catalina Moller, Carol Parra, Bastian Said, Enrique Werner, Susana Flores, Joan Villena, Alessandra Russo, Nelson Caro, Iván Montenegro and Alejandro Madrid

Molecules 2021, 26(1), 131; https://doi.org/10.3390/molecules26010131 - 30 Dec 2020

Cited by 22 | Viewed by 2982

Abstract

The aim of this study was to determine, first, the chemical composition of Aloysia polystachya (Griseb) Moldenke essential oil, from leaves harvested in central Chile; and second, its antioxidant and cytotoxic activity. Eight compounds were identified via gas chromatography–mass spectrometry (GC–MS) analyses, with [...] Read more.

The aim of this study was to determine, first, the chemical composition of Aloysia polystachya (Griseb) Moldenke essential oil, from leaves harvested in central Chile; and second, its antioxidant and cytotoxic activity. Eight compounds were identified via gas chromatography–mass spectrometry (GC–MS) analyses, with the most representative being R-carvone (91.03%), R-limonene (4.10%), and dihydrocarvone (1.07%). For Aloysia polystachya essential oil, antioxidant assays (2,2-diphenyl-1-picrylhydrazyl (DPPH), H₂O₂, ferric reducing antioxidant power (FRAP), and total reactive antioxidant potential (TRAP)) showed good antioxidant activity compared to commercial antioxidant controls; and anti-proliferative assays against three human cancer cell lines (colon, HT-29; prostate, PC-3; and breast, MCF-7) determined an IC₅₀ of 5.85, 6.74, and 9.53 µg/mL, and selectivity indices of 4.75, 4.12, and 2.92 for HT-29, PC-3, and MCF-7, respectively. We also report on assays with CCD 841 CoN (colon epithelial). Overall, results from this study may represent, in the near future, developments for natural-based cancer treatments. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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20 pages, 2164 KiB

Open AccessArticle

Chemical Composition, Antioxidant and Anticancer Activities of Leptocarpha rivularis DC Flower Extracts

by Iván Montenegro, Jorge Moreira, Ingrid Ramírez, Fernando Dorta, Elizabeth Sánchez, Juan Felipe Alfaro, Manuel Valenzuela, Carlos Jara-Gutiérrez, Ociel Muñoz, Matias Alvear, Enrique Werner, Alejandro Madrid, Joan Villena and Michael Seeger

Molecules 2021, 26(1), 67; https://doi.org/10.3390/molecules26010067 - 25 Dec 2020

Cited by 6 | Viewed by 4122

Abstract

An evaluation of antioxidant and anticancer activity was screened in Leptocarpha rivularis DC flower extracts using four solvents (n-hexane (Hex), dichloromethane (DCM), ethyl acetate (AcOEt), and ethanol (EtOH)). Extracts were compared for total extract flavonoids and phenol contents, antioxidant activity (2,2-diphenyl-1-picryl-hydrazyl-hydrate [...] Read more.

An evaluation of antioxidant and anticancer activity was screened in Leptocarpha rivularis DC flower extracts using four solvents (n-hexane (Hex), dichloromethane (DCM), ethyl acetate (AcOEt), and ethanol (EtOH)). Extracts were compared for total extract flavonoids and phenol contents, antioxidant activity (2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), ferric reducing antioxidant potential (FRAP), total reactive antioxidant properties (TRAP) and oxygen radical absorbance capacity (ORAC)) across a determined value of reduced/oxidized glutathione (GSH/GSSG), and cell viability (the sulforhodamine B (SRB) assay). The most active extracts were analyzed by chromatographic analysis (GC/MS) and tested for apoptotic pathways. Extracts from Hex, DCM and AcOEt reduced cell viability, caused changes in cell morphology, affected mitochondrial membrane permeability, and induced caspase activation in tumor cell lines HT-29, PC-3, and MCF-7. These effects were generally less pronounced in the HEK-293 cell line (nontumor cells), indicating clear selectivity towards tumor cell lines. We attribute likely extract activity to the presence of sesquiterpene lactones, in combination with other components like steroids and flavonoids. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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14 pages, 785 KiB

Open AccessArticle

Analysis of Cytotoxicity of Selected Asteraceae Plant Extracts in Real Time, Their Antioxidant Properties and Polyphenolic Profile

by Patrycja Sowa, Dana Marcinčáková, Michał Miłek, Ewelina Sidor, Jaroslav Legáth and Małgorzata Dżugan

Molecules 2020, 25(23), 5517; https://doi.org/10.3390/molecules25235517 - 25 Nov 2020

Cited by 22 | Viewed by 3868

Abstract

Plants from Asteraceae family are widely used for their therapeutic effects in the treatment of gastrointestinal diseases, but the consequences of excessive intake still need to be studied. The aims of this study were the evaluation of cytotoxicity, measurement of antioxidant properties and [...] Read more.

Plants from Asteraceae family are widely used for their therapeutic effects in the treatment of gastrointestinal diseases, but the consequences of excessive intake still need to be studied. The aims of this study were the evaluation of cytotoxicity, measurement of antioxidant properties and determination of polyphenolic profile of Tanacetum vulgare L. (tansy), Achillea millefolium L. (yarrow) and Solidago gigantea Ait. (goldenrod) ethanolic extracts. The cytotoxicity of extracts was monitored by xCELLigence system in real time by using porcine intestinal epithelial cell line (IPEC-1) and by measurement of changes in metabolic activity ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay). The antioxidant properties were measured by spectrophotometric methods and polyphenolic profiles were determined by HPLC-DAD for 50% ethanol extracts (10% w/v). Strong cytotoxic effect was recorded for tansy and yarrow extracts (125–1000 µg/mL) by xCELLigence system and MTS assay. Conversely, a supportive effect on cell proliferation was recorded for goldenrod extracts (125 µg/mL) by the same methods (p < 0.001). The antioxidant activity was in good correlation with total polyphenolic content, and the highest value was recorded for goldenrod leaves, followed by tansy leaves, goldenrod flowers and yarrow leaf extracts. The goldenrod extracts were abundant with flavonoids, whereas phenolic acid derivatives predominated in the polyphenolic profile of tansy and yarrow. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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15 pages, 2828 KiB

Open AccessArticle

Cytotoxic and Antiproliferative Effects of Diarylheptanoids Isolated from Curcuma comosa Rhizomes on Leukaemic Cells

by Natsima Viriyaadhammaa, Aroonchai Saiai, Waranya Neimkhum, Wariya Nirachonkul, Wantida Chaiyana, Sawitree Chiampanichayakul, Singkome Tima, Toyonobu Usuki, Suwit Duangmano and Songyot Anuchapreeda

Molecules 2020, 25(22), 5476; https://doi.org/10.3390/molecules25225476 - 23 Nov 2020

Cited by 7 | Viewed by 2665

Abstract

Curcuma comosa belongs to the Zingiberaceae family. In this study, two natural compounds were isolated from C. comosa, and their structures were determined using nuclear magnetic resonance. The isolated compounds were identified as 7-(3,4-dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (1) and trans-1,7-diphenyl-5-hydroxy-1-heptene [...] Read more.

Curcuma comosa belongs to the Zingiberaceae family. In this study, two natural compounds were isolated from C. comosa, and their structures were determined using nuclear magnetic resonance. The isolated compounds were identified as 7-(3,4-dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (1) and trans-1,7-diphenyl-5-hydroxy-1-heptene (2). Compound 1 showed the strongest cytotoxicity effect against HL-60 cells, while its antioxidant and anti-inflammatory properties were stronger than those of compound 2. Compound 1 proved to be a potent antioxidant, compared to ascorbic acid. Neither compounds had any effect on red blood cell haemolysis. Furthermore, compound 1 significantly decreased Wilms’ tumour 1 protein expression and cell proliferation in KG-1a cells. Compound 1 decreased the WT1 protein levels in a time- and dose- dependent manner. Compound 1 suppressed cell cycle at the S phase. In conclusion, compound 1 has a promising chemotherapeutic potential against leukaemia. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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14 pages, 2960 KiB

Open AccessArticle

Anti-Proliferative Activity of A Hydrophilic Extract of Manna from Fraxinus angustifolia Vahl through Mitochondrial Pathway-Mediated Apoptosis and Cell Cycle Arrest in Human Colon Cancer Cells

by Ignazio Restivo, Luisa Tesoriere, Anna Frazzitta, Maria Antonia Livrea, Alessandro Attanzio and Mario Allegra

Molecules 2020, 25(21), 5055; https://doi.org/10.3390/molecules25215055 - 30 Oct 2020

Cited by 5 | Viewed by 3246

Abstract

Manna is produced from the spontaneous solidification of the sap of some Fraxinus species, and, owing its content in mannitol, is used in medicine as a mild laxative. Manna is also a rich source of characteristic bio-phenols with reducing, antioxidant and anti-inflammatory properties. [...] Read more.

Manna is produced from the spontaneous solidification of the sap of some Fraxinus species, and, owing its content in mannitol, is used in medicine as a mild laxative. Manna is also a rich source of characteristic bio-phenols with reducing, antioxidant and anti-inflammatory properties. This study assesses the activity of a hydrophilic extract of manna (HME) on cellular and molecular events in human colon-rectal cancer cells. HME showed a time- and concentration-dependent anti-proliferative activity, measured by MTT assay, in all the cell lines examined, namely Caco-2, HCT-116 and HT-29. The amounts of HME that caused 50% of cell death after a 24 h treatment were 8.51 ± 0.77, 10.73 ± 1.22 and 28.92 ± 1.99 mg manna equivalents/mL, respectively; no toxicity was observed in normally differentiated Caco-2 intestinal cells. Hydroxytyrosol, a component of HME known for its cytotoxic effects on colon cancer cells, was ineffective, at least at the concentration occurring in the extract. Through flow-cytometric techniques and Western blot analysis, we show that HME treatment causes apoptosis, assessed by phosphatidylserine exposure, as well as a loss of mitochondrial membrane potential, an intracellular formation of reactive oxygen species (ROS), increases in the levels of cleaved PARP-1, caspase 3 and Bax, and a decrease in Bcl-2 expression. Moreover, HME interferes with cell cycle progression, with a block at the G1/S transition. In conclusion, the phytocomplex extracted from manna exerts an anti-proliferative activity on human colon cancer cells through the activation of mitochondrial pathway-mediated apoptosis and cell cycle arrest. Our data may suggest that manna could have the potential to exert chemo-preventive effects for the intestine. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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14 pages, 4615 KiB

Open AccessArticle

Coriolic Acid (13-(S)-Hydroxy-9Z, 11E-octadecadienoic Acid) from Glasswort (Salicornia herbacea L.) Suppresses Breast Cancer Stem Cell through the Regulation of c-Myc

by Yu-Chan Ko, Hack Sun Choi, Ji-Hyang Kim, Su-Lim Kim, Bong-Sik Yun and Dong-Sun Lee

Molecules 2020, 25(21), 4950; https://doi.org/10.3390/molecules25214950 - 26 Oct 2020

Cited by 7 | Viewed by 2606

Abstract

Cancer stem cells have certain characteristics, such as self-renewal, differentiation, and drug resistance, which are related to tumor progression, maintenance, recurrence, and metastasis. In our study, we targeted breast cancer stem cells (BCSCs) using a natural compound, coriolic acid, from Salicornia herbacea L. [...] Read more.

Cancer stem cells have certain characteristics, such as self-renewal, differentiation, and drug resistance, which are related to tumor progression, maintenance, recurrence, and metastasis. In our study, we targeted breast cancer stem cells (BCSCs) using a natural compound, coriolic acid, from Salicornia herbacea L. This compound was isolated by mammosphere formation inhibition bioassay-guided fractionation and identified by using NMR spectroscopy and electrospray ionization mass spectrometry. Coriolic acid inhibited the formation of mammospheres and induced BCSC apoptosis. It also decreased the subpopulation of CD44^high/CD24^low cells, a cancer stem cell (CSC) phenotype, and specific genes related to CSCs, such as Nanog,Oct4, and CD44. Coriolic acid decreased the transcriptional and translational levels of the c-Myc gene, which is a CSC survival factor. These results indicated that coriolic acid could be a novel compound to target BCSCs via regulation of c-Myc. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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11 pages, 1376 KiB

Open AccessArticle

Antioxidant and Cell Proliferation Properties of the Vietnamese Traditional Medicinal Plant Peltophorum pterocarpum

by Seon-Rye Kim, Dao Cuong To, Phi Hung Nguyen, Yen Nhi Nguyen, Byung-Jun Cho and Manh Hung Tran

Molecules 2020, 25(20), 4800; https://doi.org/10.3390/molecules25204800 - 19 Oct 2020

Cited by 6 | Viewed by 2547

Abstract

Peltophorum pterocarpum is regarded as one of the most important medicinal plants in the traditional medicine system of Vietnam. However, scientific evidence for the antioxidant effects against lipid peroxidation and the potential effects in cancer of this plant are lacking. In our experiments, [...] Read more.

Peltophorum pterocarpum is regarded as one of the most important medicinal plants in the traditional medicine system of Vietnam. However, scientific evidence for the antioxidant effects against lipid peroxidation and the potential effects in cancer of this plant are lacking. In our experiments, 70% ethanolic extracts of P. pterocarpum leaves (LPP) and stem bark (SPP) were evaluated for their low-density lipoprotein (LDL) oxidation and cytotoxic activity against cancer cell lines. Both LPP and SPP inhibited Cu²⁺-mediated LDL by increasing the lag time of conjugated diene formation and inhibiting the generation of thiobarbituric acid reactive substances (TBARS) in a dose-dependent manner. In cancer cells, LPP and SPP triggered the most potent cytotoxic effects against human leukemia cells, CRF-SBA and HL-60, with half-maximal inhibitory concentration (IC₅₀) values ranging from 118.5 to 157.2 µg/mL. SPP exhibited significant cytotoxicity against MIA PACA2, A549, and KG cell lines with IC₅₀ values of 167.5, 244.1 and 255.0 µg/mL, respectively. Meanwhile, LPP showed cytotoxic activity against KG with an IC₅₀ value of 228.1 µg/mL. SPP mediated cytotoxicity in HL-60 and CCRF-SBA cells through the activation of the apoptosis pathway, including the activation of caspases 3, and 9 and poly (ADP-ribose) polymerase (PARP). These results suggested that SPP may prevent the development and progression of atherosclerosis and leukemia in humans. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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14 pages, 2171 KiB

Open AccessArticle

Cytotoxicity of Oleandrin Is Mediated by Calcium Influx and by Increased Manganese Uptake in Saccharomyces cerevisiae Cells

by Lavinia L. Ruta, Claudia V. Popa and Ileana C. Farcasanu

Molecules 2020, 25(18), 4259; https://doi.org/10.3390/molecules25184259 - 17 Sep 2020

Cited by 4 | Viewed by 2458

Abstract

Oleandrin, the main component of Nerium oleander L. extracts, is a cardiotoxic glycoside with multiple pharmacological implications, having potential anti-tumoral and antiviral characteristics. Although it is accepted that the main mechanism of oleandrin action is the inhibition of Na⁺/K⁺-ATPases [...] Read more.

Oleandrin, the main component of Nerium oleander L. extracts, is a cardiotoxic glycoside with multiple pharmacological implications, having potential anti-tumoral and antiviral characteristics. Although it is accepted that the main mechanism of oleandrin action is the inhibition of Na⁺/K⁺-ATPases and subsequent increase in cell calcium, many aspects which determine oleandrin cytotoxicity remain elusive. In this study, we used the model Saccharomyces cerevisiae to unravel new elements accounting for oleandrin toxicity. Using cells expressing the Ca²⁺-sensitive photoprotein aequorin, we found that oleandrin exposure resulted in Ca²⁺ influx into the cytosol and that failing to pump Ca²⁺ from the cytosol to the vacuole increased oleandrin toxicity. We also found that oleandrin exposure induced Mn²⁺ accumulation by yeast cells via the plasma membrane Smf1 and that mutants with defects in Mn²⁺ homeostasis are oleandrin-hypersensitive. Our data suggest that combining oleandrin with agents which alter Ca²⁺ or Mn²⁺ uptake may be a way of controlling oleandrin toxicity. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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19 pages, 4338 KiB

Open AccessArticle

Cyperus articulatus L. (Cyperaceae) Rhizome Essential Oil Causes Cell Cycle Arrest in the G₂/M Phase and Cell Death in HepG2 Cells and Inhibits the Development of Tumors in a Xenograft Model

by Mateus L. Nogueira, Emilly J. S. P. de Lima, Asenate A. X. Adrião, Sheila S. Fontes, Valdenizia R. Silva, Luciano de S. Santos, Milena B. P. Soares, Rosane B. Dias, Clarissa A. Gurgel Rocha, Emmanoel V. Costa, Felipe M. A. da Silva, Marcos A. Vannier-Santos, Nállarett M. D. Cardozo, Hector H. F. Koolen and Daniel P. Bezerra

Molecules 2020, 25(11), 2687; https://doi.org/10.3390/molecules25112687 - 09 Jun 2020

Cited by 15 | Viewed by 4088

Abstract

Cyperus articulatus L. (Cyperaceae), popularly known in Brazil as “priprioca” or “piriprioca”, is a tropical and subtropical plant used in popular medical practices to treat many diseases, including cancer. In this study, C. articulatus rhizome essential oil (EO), collected from the Brazilian Amazon [...] Read more.

Cyperus articulatus L. (Cyperaceae), popularly known in Brazil as “priprioca” or “piriprioca”, is a tropical and subtropical plant used in popular medical practices to treat many diseases, including cancer. In this study, C. articulatus rhizome essential oil (EO), collected from the Brazilian Amazon rainforest, was addressed in relation to its chemical composition, induction of cell death in vitro and inhibition of tumor development in vivo, using human hepatocellular carcinoma HepG2 cells as a cell model. EO was obtained by hydrodistillation using a Clevenger-type apparatus and characterized qualitatively and quantitatively by gas chromatography coupled to mass spectrometry (GC-MS) and gas chromatography with flame ionization detection (GC-FID), respectively. The cytotoxic activity of EO was examined against five cancer cell lines (HepG2, HCT116, MCF-7, HL-60 and B16-F10) and one non-cancerous one (MRC-5) using the Alamar blue assay. Cell cycle distribution and cell death were investigated using flow cytometry in HepG2 cells treated with EO after 24, 48 and 72 h of incubation. The cells were also stained with May–Grunwald–Giemsa to analyze the morphological changes. The anti-liver-cancer activity of EO in vivo was evaluated in C.B-17 severe combined immunodeficient (SCID) mice with HepG2 cell xenografts. The main representative substances of this EO sample were muskatone (11.6%), cyclocolorenone (10.3%), α-pinene (8.26%), pogostol (6.36%), α-copaene (4.83%) and caryophyllene oxide (4.82%). EO showed IC₅₀ values for cancer cell lines ranging from 28.5 µg/mL for HepG2 to >50 µg/mL for HCT116, and an IC₅₀ value for non-cancerous of 46.0 µg/mL (MRC-5), showing selectivity indices below 2-fold for all cancer cells tested. HepG2 cells treated with EO showed cell cycle arrest at G₂/M along with internucleosomal DNA fragmentation. The morphological alterations included cell shrinkage and chromatin condensation. Treatment with EO also increased the percentage of apoptotic-like cells. The in vivo tumor mass inhibition rates of EO were 46.5–50.0%. The results obtained indicate the anti-liver-cancer potential of C. articulatus rhizome EO. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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18 pages, 2538 KiB

Open AccessArticle

Cytotoxic Activity of Christia vespertilionis Root and Leaf Extracts and Fractions against Breast Cancer Cell Lines

by Joanna Jinling Lee, Latifah Saiful Yazan, Nur Kartinee Kassim, Che Azurahanim Che Abdullah, Nurulaidah Esa, Pei Cee Lim and Dai Chuan Tan

Molecules 2020, 25(11), 2610; https://doi.org/10.3390/molecules25112610 - 04 Jun 2020

Cited by 20 | Viewed by 5266

Abstract

Christia vespertilionis, commonly known as ‘Daun Rerama’, has recently garnered attention from numerous sources in Malaysia as an alternative treatment. Its herbal decoction was believed to show anti-inflammatory and anti-cancer effects. The present study investigated the cytotoxicity of the extract of root [...] Read more.

Christia vespertilionis, commonly known as ‘Daun Rerama’, has recently garnered attention from numerous sources in Malaysia as an alternative treatment. Its herbal decoction was believed to show anti-inflammatory and anti-cancer effects. The present study investigated the cytotoxicity of the extract of root and leaf of C. vespertilionis. The plant parts were successively extracted using the solvent maceration method. The most active extract was further fractionated to afford F1–F8. The cytotoxic effects were determined using MTT assay against human breast carcinoma cell lines (MCF-7 and MDA-MB-231). The total phenolic content (TPC) of the extracts were determined. The antioxidant properties of the extract were also studied using DPPH and β-carotene bleaching assays. The ethyl acetate root extract demonstrated selective cytotoxicity especially against MDA-MB-231 with the highest TPC and antioxidant properties compared to others (p < 0.05). The TPC and antioxidant results suggest the contribution of phenolic compounds toward its antioxidant strength leading to significant cytotoxicity. F3 showed potent cytotoxic effects while F4 showed better antioxidative strength compared to others (p < 0.05). Qualitative phytochemical screening of the most active fraction, F3, suggested the presence of flavonoids, coumarins and quinones to be responsible toward the cytotoxicity. The study showed the root extracts of C. vespertilionis to possess notable anti-breast cancer effects. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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18 pages, 1709 KiB

Open AccessArticle

Antioxidant Effects, Antiproliferative Effects, and Molecular Docking of Clinacanthus nutans Leaf Extracts

by Noor Zafirah Ismail, Zaleha Md Toha, Musthahimah Muhamad, Nik Nur Syazni Nik Mohamed Kamal, Nur Nadhirah Mohamad Zain and Hasni Arsad

Molecules 2020, 25(9), 2067; https://doi.org/10.3390/molecules25092067 - 29 Apr 2020

Cited by 25 | Viewed by 5493

Abstract

Clinacanthus nutans is a well-known herb that has been used as an alternative and therapeutic medicine, however more selective C. nutans extracts are needed. In this study, leaves were extracted with 80% methanol and further fractionated with n-hexane, dichloromethane, chloroform, n-butanol, and [...] Read more.

Clinacanthus nutans is a well-known herb that has been used as an alternative and therapeutic medicine, however more selective C. nutans extracts are needed. In this study, leaves were extracted with 80% methanol and further fractionated with n-hexane, dichloromethane, chloroform, n-butanol, and aqueous residue. Subsequently, the total phenolic content (TPC), total flavonoid content (TFC), antioxidant scavenging activity, and antiproliferative effects on breast cancer (Michigan Cancer Foundation-7 [MCF7]) and normal breast (Michigan Cancer Foundation-10A [MCF 10A]) cells of the extracts were measured. Additionally, molecular docking simulation of the major compounds from C. nutans extracts was conducted. The aqueous residue had the highest TPC and TFC, whereas the crude extract had the highest scavenging activity. Among the extracts, dichloromethane extract (CN-Dcm) was selected as it had the highest selectivity index (SI) (1.48). Then, the chosen extract (CN-Dcm) was proceed for further analysis. The compounds from CN-Dcm were identified using gas chromatography–mass spectrometry (GC-MS). The major compounds from CN-Dcm were further investigated through molecular docking studies. Palmitic acid and linolenyl alcohol were the compounds found in the CN-Dcm extract that exhibited the highest binding affinities with p53-binding protein Mdm-2. These results highlight the potential of C. nutans as a source of anticancer activities. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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12 pages, 3405 KiB

Open AccessCommunication

Aviculin Isolated from Lespedeza cuneata Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway

by Dahae Lee, Yong Hoon Lee, Kwang Ho Lee, Bum Soo Lee, Akida Alishir, Yoon-Joo Ko, Ki Sung Kang and Ki Hyun Kim

Molecules 2020, 25(7), 1708; https://doi.org/10.3390/molecules25071708 - 08 Apr 2020

Cited by 12 | Viewed by 3538

Abstract

The global incidence of breast cancer has increased. However, there are many impediments to the development of safe and effective anticancer drugs. The aim of the present study was to evaluate the effect of aviculin isolated from Lespedeza cuneata (Dum. Cours.) G. Don. [...] Read more.

The global incidence of breast cancer has increased. However, there are many impediments to the development of safe and effective anticancer drugs. The aim of the present study was to evaluate the effect of aviculin isolated from Lespedeza cuneata (Dum. Cours.) G. Don. (Fabaceae) on MCF-7 human breast cancer cells and determine the underlying mechanism. Using the bioassay-guided isolation by water soluble tetrazolium salt (WST-1)-based Ez-Cytox assay, nine compounds (four lignan glycosides (1–4), three flavonoid glycosides (5–7), and two phenolic compounds (8 and 9)) were isolated from the ethyl acetate (EA) fraction of the L. cuneata methanolic extract. Of these, aviculin (2), a lignan glycoside, was the only compound that reduced metabolic activity on MCF-7 cells below 50% (IC₅₀: 75.47 ± 2.23 μM). The underlying mechanism was analyzed using the annexin V Alexa Fluor 488 binding assay and Western blotting. Aviculin (2) was found to induce apoptotic cell death through the intrinsic apoptosis pathway, as indicated by the increased expression of initiator caspase-9, executioner caspase-7, and poly (ADP-ribose) polymerase (PARP). Aviculin (2)-induced apoptotic cell death was accompanied by an increase in the Bax/Bcl-2 ratio. These findings demonstrated that aviculin (2) could induce breast cancer cell apoptosis through the intrinsic apoptosis pathway, and it can therefore be considered an excellent candidate for herbal treatment of breast cancer. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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19 pages, 1211 KiB

Open AccessArticle

Synthesis and Bioactivity Assessment of Novel Spiro Pyrazole-Oxindole Congeners Exhibiting Potent and Selective in vitro Anticancer Effects

by Heba M. Abo-Salem, Amr Nassrallah, Ahmed A.F. Soliman, Manal S. Ebied, Mohamed E. Elawady, Sayeda A. Abdelhamid, Eslam R. El-Sawy, Yazeed A. Al-Sheikh and Mourad A. M. Aboul-Soud

Molecules 2020, 25(5), 1124; https://doi.org/10.3390/molecules25051124 - 03 Mar 2020

Cited by 18 | Viewed by 3785

Abstract

The present work aims to design and synthesize novel series of spiro pyrazole-3,3’-oxindoles analogues and investigate their bioactivity as antioxidant and antimicrobial agents, as well as antiproliferative potency against selected human cancerous cell lines (i.e., breast, MCF-7; colon, HCT-116 and liver, HepG-2) relative [...] Read more.

The present work aims to design and synthesize novel series of spiro pyrazole-3,3’-oxindoles analogues and investigate their bioactivity as antioxidant and antimicrobial agents, as well as antiproliferative potency against selected human cancerous cell lines (i.e., breast, MCF-7; colon, HCT-116 and liver, HepG-2) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and proapoptotic protein markers. The analytical and spectral data of the all synthesized target congeners were compatible with their structures. Synthesized compounds showed diverse moderate to powerful antimicrobial and antioxidant activities. Results of MTT assay revealed that seven synthesized compounds (i.e., 11a, 11b, 12a, 12b, 13b, 13c and 13h) particularly exhibited significant cytotoxicity against the three cancerous cell lines under investigation. Ranges of IC₅₀ values obtained were 5.7–21.3 and 5.8–37.4 µg/mL against HCT-116 and MCF-7, respectively; which is 3.8 and 6.5-fold (based on the least IC₅₀ values) more significant relative to the reference chemotherapeutic drug doxorubicin. In HepG-2 cells, the analogue 13h exhibited the highest cytotoxicity with IC₅₀ value of 19.2µg/mL relative to doxorubicin (IC₅₀ = 21.6µg/mL). The observed cytotoxicity was specific to cancerous cells, as evidenced by the minimal toxicity in the noncancerous control skin-fibroblast cells. ELISA results indicated that the observed antiproliferative effect against examined cancer cell lines is mediated via engaging the activation of apoptosis as illustrated by the significant increase in proapoptotic protein markers (p53, bax and caspase-3) and reduction in the antiapoptotic marker bcl-2. Taken together, results of the present study emphasize the potential of spiro pyrazole-oxindole analogues as valuable candidate anticancer agents against human cancer cells. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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19 pages, 2102 KiB

Open AccessArticle

Pharmacological Evaluation of the Anticancer Activity of Extracts and Fractions of Lannea barteri Oliv. (Anacardiaceae) on Adherent Human Cancer Cell Lines

by Florence N. Mbaoji, Steven Behnisch-Cornwell, Adaobi C. Ezike, Chukwuemeka S. Nworu and Patrick J. Bednarski

Molecules 2020, 25(4), 849; https://doi.org/10.3390/molecules25040849 - 14 Feb 2020

Cited by 6 | Viewed by 3393

Abstract

In western Africa ethnomedicine, Lannea barteri Oliv. (Anacardiaceae) is believed to have activity against gastrointestinal, neurological and endocrine diseases. Previous studies on this plant have revealed antimicrobial, anticholinestrase, anticonvulsant, antioxidant and anti-inflammatory activities. However, the anticancer potential of L. barteri has not been [...] Read more.

In western Africa ethnomedicine, Lannea barteri Oliv. (Anacardiaceae) is believed to have activity against gastrointestinal, neurological and endocrine diseases. Previous studies on this plant have revealed antimicrobial, anticholinestrase, anticonvulsant, antioxidant and anti-inflammatory activities. However, the anticancer potential of L. barteri has not been studied to date. The aim of this study was to evaluate the anticancer potential of hot and cold extracts and silica gel column chromatographic fractions of L. barteri leaf and stem bark. The extracts and fractions were tested for anticancer activity by using the crystal violet cell proliferation assay on four adherent human carcinoma cell lines—5637 (bladder), KYSE 70 (oesophagus), SiSo (cervical) and HepG2 (hepatic). The inhibitory concentration (IC₅₀) of fractions IH, 1I, 2E and 2F were: 3.75 ± 1.33, 3.88 ± 2.15, 0.53 ± 0.41, and 0.42 ± 0.45 µg/mL against KYSE 70 and 1.04 ± 0.94, 2.69 ± 1.17, 2.38 ± 3.64, 2.17 ± 1.92 µg/mL against SiSo cell lines respectively. Fraction 2E showed weak apoptotic activity at double the IC₅₀ and some sign of cell cycle arrest in the G2/M phase. Thus, phytoconstituents of L. barteri leaf and stem bark can inhibit the proliferation of cancer cell lines indicating the presence of possible anticancer agents in this plant. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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30 pages, 6408 KiB

Open AccessArticle

Potential of Thai Herbal Extracts on Lung Cancer Treatment by Inducing Apoptosis and Synergizing Chemotherapy

by Juthathip Poofery, Patompong Khaw-on, Subhawat Subhawa, Bungorn Sripanidkulchai, Apichat Tantraworasin, Somcharoen Saeteng, Sopon Siwachat, Nirush Lertprasertsuke and Ratana Banjerdpongchai

Molecules 2020, 25(1), 231; https://doi.org/10.3390/molecules25010231 - 06 Jan 2020

Cited by 25 | Viewed by 8111

Abstract

The incidence of lung cancer has increased while the mortality rate has continued to remain high. Effective treatment of this disease is the key to survival. Therefore, this study is a necessity in continuing research into new effective treatments. In this study we [...] Read more.

The incidence of lung cancer has increased while the mortality rate has continued to remain high. Effective treatment of this disease is the key to survival. Therefore, this study is a necessity in continuing research into new effective treatments. In this study we determined the effects of three different Thai herbs on lung cancer. Bridelia ovata, Croton oblongifolius, and Erythrophleum succirubrum were extracted by ethyl acetate and 50% ethanol. The cytotoxicity was tested with A549 lung cancer cell line. We found four effective extracts that exhibited toxic effects on A549 cells. These extracts included ethyl acetate extracts of B. ovata (BEA), C. oblongifolius (CEA), and E. succirubrum (EEA), and an ethanolic extract of E. succirubrum (EE). Moreover, these effective extracts were tested in combination with chemotherapeutic drugs. An effective synergism of these treatments was found specifically through a combination of BEA with methotrexate, EE with methotrexate, and EE with etoposide. Apoptotic cell death was induced in A549 cells by these effective extracts via the mitochondria-mediated pathway. Additionally, we established primary lung cancer and normal epithelial cells from lung tissue of lung cancer patients. The cytotoxicity results showed that EE had significant potential to be used for lung cancer treatment. In conclusion, the four effective extracts possessed anticancer effects on lung cancer. The most effective extract was found to be E. succirubrum (EE). Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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15 pages, 2778 KiB

Open AccessArticle

Chelerythrine Chloride Downregulates β-Catenin and Inhibits Stem Cell Properties of Non-Small Cell Lung Carcinoma

by Win Sen Heng and Shiau-Chuen Cheah

Molecules 2020, 25(1), 224; https://doi.org/10.3390/molecules25010224 - 06 Jan 2020

Cited by 30 | Viewed by 3865

Abstract

Plant secondary metabolites have been seen as alternatives to seeking new medicines for treating various diseases. Phytochemical scientists remain hopeful that compounds isolated from natural sources could help alleviate the leading problem in oncology—the lung malignancy that kills an estimated two million people [...] Read more.

Plant secondary metabolites have been seen as alternatives to seeking new medicines for treating various diseases. Phytochemical scientists remain hopeful that compounds isolated from natural sources could help alleviate the leading problem in oncology—the lung malignancy that kills an estimated two million people annually. In the present study, we characterized a medicinal compound benzophenanthridine alkaloid, called chelerythrine chloride for its anti-tumorigenic activities. Cell viability assays confirmed its cytotoxicity and anti-proliferative activity in non-small cell lung carcinoma (NSCLC) cell lines. Immunofluorescence staining of β-catenin revealed that there was a reduction of nuclear content as well as overall cellular content of β-catenin after treating NCI-H1703 with chelerythrine chloride. In functional characterizations, we observed favorable inhibitory activities of chelerythrine chloride in cancer stem cell (CSC) properties, which include soft agar colony-forming, migration, invasion, and spheroid forming abilities. Interesting observations in chelerythrine chloride treatment noted that its action abides to certain concentration-specific-targeting behavior in modulating β-catenin expression and apoptotic cell death. The downregulation of β-catenin implicates the downregulation of CSC transcription factors like SOX2 and MYC. In conclusion, chelerythrine chloride has the potential to mitigate cancer growth due to inhibitory actions toward the tumorigenic activity of CSC in lung cancer and it can be flexibly adjusted according to concentration to modulate specific targeting in different cell lines. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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13 pages, 2286 KiB

Open AccessArticle

Coagulant Effects and Mechanism of Schefflera heptaphylla (L.) Frodin

by Xuqiang Liu, Jing Dong, Qiongxin Liang, Hui-min David Wang, Zhenhua Liu, Ruian Xu and Wenyi Kang

Molecules 2019, 24(24), 4547; https://doi.org/10.3390/molecules24244547 - 12 Dec 2019

Cited by 6 | Viewed by 3392

Abstract

Schefflera heptaphylla (L.) Frodin, are commonly used in anti-inflammatory, analgesic, traumatic bleeding and hemostasisas. In this paper, the coagulation effect of the ethanol extract (Set), ethyl acetate phase (Sea) and n-butanol phase (Sbu) was evaluated by prothrombin time (PT), activated partial thromboplastin [...] Read more.

Schefflera heptaphylla (L.) Frodin, are commonly used in anti-inflammatory, analgesic, traumatic bleeding and hemostasisas. In this paper, the coagulation effect of the ethanol extract (Set), ethyl acetate phase (Sea) and n-butanol phase (Sbu) was evaluated by prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen content (FIB) assays in vitro. Then, Three main lupanine triterpenes (compounds A–C) were isolated and identified from Sea and Sbu by a bioassay-guided method and their structure were identified as 3α-Hydroxy-lup-20(29)-ene-23, 28-dioic acid, betulinic acid 3-O-sulfate and 3α-Hydroxy-lup-20(29)-ene-23, 28-dioic acid 28-O-(α-l-rhamnopyranosyl(1→4)-O-β-d-glucopyranosyl(1→6))-β-d-glucopyranoside) by spectroscopic data analysis. Among of them, compound B was confirmed to have significant coagulant effect in vitro. Furthermore, the pro-coagulation mechanism of S. heptaphylla extracts and compound B were investigated by measuring whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentetion rate (ESR), pack cell volume (PCV), APTT, PT, TT, and FIB in vivo. Meanwhile, the levels of thromboxane B₂ (TXB₂), 6-keto prostaglandin F_1α (6-keto-PGF_1α), endothelial nitric oxide synthase (eNOS) and (endothelin-1) ET-1 were detected. The bleeding time (BT) was tested by tail bleeding method, which proved the traumatic bleeding and hemostasis activities of S. heptaphylla. The pharmacology experiments showed that the Set, Sea, Sbu and compound B has significant pro-coagulation effect. In addition, compound B might be the main constituent of pro-coagulation in S. heptaphylla These results could support the fact that S. heptaphylla could be used traditionally to cure traumatic bleeding, and the pro-coagulation effects were associated with the regulation of vascular endothelium active substance and hemorheology parameters. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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14 pages, 4099 KiB

Open AccessArticle

Retrochalcone Echinatin Triggers Apoptosis of Esophageal Squamous Cell Carcinoma via ROS- and ER Stress-Mediated Signaling Pathways

by Ah-Won Kwak, Joon-Seok Choi, Mee-Hyun Lee, Ha-Na Oh, Seung-Sik Cho, Goo Yoon, Kangdong Liu, Jung-Il Chae and Jung-Hyun Shim

Molecules 2019, 24(22), 4055; https://doi.org/10.3390/molecules24224055 - 09 Nov 2019

Cited by 31 | Viewed by 3089

Abstract

Esophageal squamous cell carcinoma (ESCC) is a poor prognostic cancer with a low five-year survival rate. Echinatin (Ech) is a retrochalone from licorice. It has been used as a herbal medicine due to its anti-inflammatory and anti-oxidative effects. However, its anticancer activity or [...] Read more.

Esophageal squamous cell carcinoma (ESCC) is a poor prognostic cancer with a low five-year survival rate. Echinatin (Ech) is a retrochalone from licorice. It has been used as a herbal medicine due to its anti-inflammatory and anti-oxidative effects. However, its anticancer activity or underlying mechanism has not been elucidated yet. Thus, the objective of this study was to investigate the anti-tumor activity of Ech on ESCC by inducing ROS and ER stress dependent apoptosis. Ech inhibited ESCC cell growth in anchorage-dependent and independent analysis. Treatment with Ech induced G2/M phase of cell cycle and apoptosis of ESCC cells. It also regulated their related protein markers including p21, p27, cyclin B1, and cdc2. Ech also led to phosphorylation of JNK and p38. Regarding ROS and ER stress formation associated with apoptosis, we found that Ech increased ROS production, whereas its increase was diminished by NAC treatment. In addition, ER stress proteins were induced by treatment with Ech. Moreover, Ech enhanced MMP dysfunction and caspases activity. Furthermore, it regulated related biomarkers. Taken together, our results suggest that Ech can induce apoptosis in human ESCC cells via ROS/ER stress generation and p38 MAPK/JNK activation. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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10 pages, 1409 KiB

Open AccessArticle

Five New Meroterpenoids from the Fruiting Bodies of the Basidiomycete Clitocybe clavipes with Cytotoxic Activity

by Zhaocui Sun, Xudong Xu, Hanqiao Liang, Xinyi Xia, Guoxu Ma and Leiling Shi

Molecules 2019, 24(22), 4015; https://doi.org/10.3390/molecules24224015 - 06 Nov 2019

Cited by 10 | Viewed by 2202

Abstract

Five new meroterpenoids, clavipols A–B (1–2) with a 12-membered ether ring and clavilactones G–I (3–5) having a 10-membered carbocycle connected to a hydroquinone and an α,β-epoxy/unsaturated lactone, were obtained from the fruiting bodies of the [...] Read more.

Five new meroterpenoids, clavipols A–B (1–2) with a 12-membered ether ring and clavilactones G–I (3–5) having a 10-membered carbocycle connected to a hydroquinone and an α,β-epoxy/unsaturated lactone, were obtained from the fruiting bodies of the basidiomycete Clitocybe clavipes. Their structures were determined by comprehensive analysis of their spectroscopic data, and the absolute configuration of 1 was established by quantum chemical calculations of electronic circular dichroism (ECD). All the isolated compounds (1–5) were tested for their cytotoxic activity against three human tumor cell lines (Hela, SGC-7901, and SHG-44) in vitro after treatment for 48 h. Compound 4 exhibited moderate cytotoxic activity against Hela and SGC-7901 tumor cell lines, with IC₅₀ values of 23.5 and 14.5 µM, respectively. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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22 pages, 6620 KiB

Open AccessArticle

Differential Cytotoxic Potential of Acridocarpus orientalis Leaf and Stem Extracts with the Ability to Induce Multiple Cell Death Pathways

by Sameera Omar Mohammed Saeed Balhamar, Neena Gopinathan Panicker, Shaima Akhlaq, Mohammed Mansoor Qureshi, Waqar Ahmad, Najeeb Ur Rehman, Liaqat Ali, Ahmed Al-Harrasi, Javid Hussain and Farah Mustafa

Molecules 2019, 24(21), 3976; https://doi.org/10.3390/molecules24213976 - 03 Nov 2019

Cited by 8 | Viewed by 4220

Abstract

This study systematically analyzed the anticancer potential of Acridocarpus orientalis (AO), a traditional medicinal plant of the Arabian Peninsula/East Africa known for its anti-inflammatory and pain relief properties. Tests of serial organic fractions from methanolic extracts of its leaves and stems revealed that [...] Read more.

This study systematically analyzed the anticancer potential of Acridocarpus orientalis (AO), a traditional medicinal plant of the Arabian Peninsula/East Africa known for its anti-inflammatory and pain relief properties. Tests of serial organic fractions from methanolic extracts of its leaves and stems revealed that only some fractions showed anti-proliferative potential with the dichloromethane fraction from leaves (AOD (L)) showing the most cytotoxic effect against both breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancer cell lines. The n-butanol fraction from the stems (AOB (S)), on the other hand, was more effective against cervical cancer cells and did not harm the normal cells. Further characterization of the mode of cell killing revealed that AOD (L) depended more on non-apoptotic pathways for its cytotoxicity in breast cancer cells, while it could activate some apoptosis and necroptosis in HeLa cells. The AOB (S) fraction could primarily activate apoptosis and some necroptosis in HeLa cells. Both fractions perturbed autophagy, but in a dissimilar manner. Thus, different parts of A. orientalis revealed variable potential to induce cell death in cancer cells via apoptotic and non-apoptotic pathways, making A. orientalis a valuable plant for the exploration of anticancer bioactive reagents, some of which may be protective for normal cells. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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16 pages, 4918 KiB

Open AccessArticle

Apoptotic Induction and Anti-Migratory Effects of Rhazya Stricta Fruit Extracts on a Human Breast Cancer Cell Line

by Mohammed Al-Zharani, Fahd A. Nasr, Nael Abutaha, Ali S. Alqahtani, Omar M. Noman, Mohammed Mubarak and Muhammad A. Wadaan

Molecules 2019, 24(21), 3968; https://doi.org/10.3390/molecules24213968 - 01 Nov 2019

Cited by 28 | Viewed by 5119

Abstract

Rhazya stricta is a medicinal plant that is widely used in Saudi folklore medicine for treatment of various diseases. R. stricta fruit powder was sequentially extracted with n-hexane, chloroform, ethyl acetate, and methanol using a Soxhlet extractor. The cytotoxic effects of these [...] Read more.

Rhazya stricta is a medicinal plant that is widely used in Saudi folklore medicine for treatment of various diseases. R. stricta fruit powder was sequentially extracted with n-hexane, chloroform, ethyl acetate, and methanol using a Soxhlet extractor. The cytotoxic effects of these fractions on human breast cancer cells (MDA-MB-231 and MCF-7) and non-tumorigenic control cells (MCF-10A) were evaluated via cell viability measurements, microscopy, gene expression, and migration assays. Moreover, the effect of the most promising extract on 7,12-dimethyl-benz[a]anthracene (DMBA)-induced breast cancer was investigated in rats. The promising extract was also subjected to gas chromatography–mass spectrometry. Fruit extracts of R. stricta were significantly cytotoxic toward all tested cell lines, as demonstrated by MTT and LDH assays. Treatment of MDA-MB-231 cells with fruit ethyl acetate fraction (RSF EtOAc) increased expression 11of P53, Bax and activation of caspase 3/7. A cell migration scratch assay demonstrated that extracts at non-cytotoxic concentrations exerted a potent anti-migration activity against the highly invasive MDA-MB-231 cell line. Moreover, RT-PCR results showed that RSF EtOAc significantly downregulated MMP-2 and MMP-9 expression, which play an important role in breast cancer metastasis. Histological studies of breast tissue in experimental animals showed a slight improvement in tissue treated with fruit ethyl acetate extract. GC-MS chromatogram showed thirteen peaks with major constituents were camphor, trichosenic acid and guanidine. Our current study demonstrates that fruit extracts of R. stricta are cytotoxic toward breast cancer cell lines through apoptotic mechanisms. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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16 pages, 5084 KiB

Open AccessArticle

Two Novel Polysaccharides in Psoralea corylifolia L and anti-A549 Lung Cancer Cells Activity In Vitro

by Zhenhua Yin, Wei Zhang, Juanjuan Zhang, Huili Liu, Qingfeng Guo, Lin Chen, Jinmei Wang and Wenyi Kang

Molecules 2019, 24(20), 3733; https://doi.org/10.3390/molecules24203733 - 16 Oct 2019

Cited by 11 | Viewed by 3826

Abstract

Two novel water soluble heteroglycan (PCp-I and PCp-II) with anti-A549 lung cancer cells activity were isolated from Psoralea corylifolia L. Their average molecular weights were 2.721 × 10⁴ and 2.850 × 10⁴. PCp-I and PCp-II had the same monosaccharide composition, [...] Read more.

Two novel water soluble heteroglycan (PCp-I and PCp-II) with anti-A549 lung cancer cells activity were isolated from Psoralea corylifolia L. Their average molecular weights were 2.721 × 10⁴ and 2.850 × 10⁴. PCp-I and PCp-II had the same monosaccharide composition, but their molar ratios were different. Based on methylation and NMR spectroscopy, the part structure of PCp-I was identified. The results of scanning electron microscope (SEM) showed that PCp-I had an irregular porous structure and PCp-II was flaky and irregularly curved. The results of thermogravimetry-differential scanning calorimetry (TG-DSC) showed that PCp-I and PCp-II had good thermal stability. Furthermore, PCp-I and PCp-II exhibited significant anti-A549 lung cancer cells activity (IC₅₀ = 64.84 and 126.30 μM) in vitro. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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13 pages, 5249 KiB

Open AccessArticle

After In Vitro Digestion, Jackfruit Flake Affords Protection against Acrylamide-Induced Oxidative Damage

by Daofeng Qu, Chu Liu, Mengxue Jiang, Lifang Feng, Yuewen Chen and Jianzhong Han

Molecules 2019, 24(18), 3322; https://doi.org/10.3390/molecules24183322 - 12 Sep 2019

Cited by 8 | Viewed by 2422

Abstract

Some studies have demonstrated that acrylamide (AA) was correlated with oxidative stress, resulting in physical damage. The jackfruit flake was an immature pulp that contained a high level of antioxidant activity. This study aimed to assess the defensive efficacy of jackfruit flake in [...] Read more.

Some studies have demonstrated that acrylamide (AA) was correlated with oxidative stress, resulting in physical damage. The jackfruit flake was an immature pulp that contained a high level of antioxidant activity. This study aimed to assess the defensive efficacy of jackfruit flake in AA-induced oxidative stress before and after simulated gastrointestinal digestion. Our results indicate that the total polyphenol content of Jackfruit flake digest (Digestive products of jackfruit flake after gastrointestinal, JFG) was diminished; however, JFG had raised the relative antioxidant capacity compared to Jackfruit flake extract (JFE). Additionally, the results of High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) implied that a proportion of compounds were degraded/converted into other unknown and/or undetected metabolites. Further, by high content analysis (HCA) techniques, JFG markedly reduced cytotoxicity and excessive production of reactive oxygen species (ROS) in cells, thereby alleviating mitochondrial disorders. In this study, it may be converted active compounds after digestion that had preferable protective effects against AA-induced oxidative damage. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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12 pages, 2607 KiB

Open AccessArticle

Paradoxical Patterns of Sinusoidal Obstruction Syndrome-Like Liver Injury in Aged Female CD-1 Mice Triggered by Cannabidiol-Rich Cannabis Extract and Acetaminophen Co-Administration

by Laura E. Ewing, Mitchell R. McGill, Eric U. Yee, Charles M. Quick, Charles M. Skinner, Stefanie Kennon-McGill, Melissa Clemens, Joel H. Vazquez, Sandra S. McCullough, D. Keith Williams, Kristy R. Kutanzi, Larry A. Walker, Mahmoud A. ElSohly, Laura P. James, Bill J. Gurley and Igor Koturbash

Molecules 2019, 24(12), 2256; https://doi.org/10.3390/molecules24122256 - 17 Jun 2019

Cited by 19 | Viewed by 7889

Abstract

The goal of this study was to investigate the potential for a cannabidiol-rich cannabis extract (CRCE) to interact with the most common over-the-counter drug and the major known cause of drug-induced liver injury–acetaminophen (APAP)–in aged female CD-1 mice. Gavaging mice with 116 mg/kg [...] Read more.

The goal of this study was to investigate the potential for a cannabidiol-rich cannabis extract (CRCE) to interact with the most common over-the-counter drug and the major known cause of drug-induced liver injury–acetaminophen (APAP)–in aged female CD-1 mice. Gavaging mice with 116 mg/kg of cannabidiol (CBD) [mouse equivalent dose (MED) of 10 mg/kg of CBD] in CRCE delivered with sesame oil for three consecutive days followed by intraperitoneally (i.p.) acetaminophen (APAP) administration (400 mg/kg) on day 4 resulted in overt toxicity with 37.5% mortality. No mortality was observed in mice treated with 290 mg/kg of CBD+APAP (MED of 25 mg/kg of CBD) or APAP alone. Following CRCE/APAP co-administration, microscopic examination revealed a sinusoidal obstruction syndrome-like liver injury–the severity of which correlated with the degree of alterations in physiological and clinical biochemistry end points. Mechanistically, glutathione depletion and oxidative stress were observed between the APAP-only and co-administration groups, but co-administration resulted in much greater activation of c-Jun N-terminal kinase (JNK). Strikingly, these effects were not observed in mice gavaged with 290 mg/kg CBD in CRCE followed by APAP administration. These findings highlight the potential for CBD/drug interactions, and reveal an interesting paradoxical effect of CBD/APAP-induced hepatotoxicity. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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19 pages, 2290 KiB

Open AccessArticle

Comparative Analysis of Pentacyclic Triterpenic Acid Compositions in Oleogum Resins of Different Boswellia Species and Their In Vitro Cytotoxicity against Treatment-Resistant Human Breast Cancer Cells

by Michael Schmiech, Sophia J. Lang, Katharina Werner, Luay J. Rashan, Tatiana Syrovets and Thomas Simmet

Molecules 2019, 24(11), 2153; https://doi.org/10.3390/molecules24112153 - 07 Jun 2019

Cited by 27 | Viewed by 8678

Abstract

Pentacyclic triterpenic acids from oleogum resins of Boswellia species are of considerable therapeutic interest. Yet, their pharmaceutical development is hampered by uncertainties regarding botanical identification and the complexity of triterpenic acid mixtures. Here, a highly sensitive, selective, and accurate method for the simultaneous [...] Read more.

Pentacyclic triterpenic acids from oleogum resins of Boswellia species are of considerable therapeutic interest. Yet, their pharmaceutical development is hampered by uncertainties regarding botanical identification and the complexity of triterpenic acid mixtures. Here, a highly sensitive, selective, and accurate method for the simultaneous quantification of eight boswellic and lupeolic acids by high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS) was developed. The method was applied to the comparative analysis of 41 oleogum resins of the species B. sacra, B. dalzielli, B. papyrifera, B. serrata, B. carterii, B. neglecta, B. rivae, B. frereana, and B. occulta. Multivariate statistical analysis of the data revealed differences in the triterpenic acid composition that could be assigned to distinct Boswellia species and to their geographic growth location. Extracts of the oleogum resins exhibited cytotoxicity against the human, treatment-resistant, metastatic breast cancer cell line MDA-MB-231. Extracts from B. sacra were the most potent ones with an average IC₅₀ of 8.3 ± 0.6 µg/mL. The oleogum resin of the B. sacra was further fractionated to enrich different groups of substances. The cytotoxic efficacy against the cancer cells correlates positively with the contents of pentacyclic triterpenic acids in Boswellia extracts. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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Review

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18 pages, 1244 KiB

Open AccessReview

Toxicity and Anticancer Potential of Karwinskia: A Review

by Gilberto Jaramillo-Rangel, María-de-Lourdes Chávez-Briones, Alberto Niderhauser-García and Marta Ortega-Martínez

Molecules 2020, 25(23), 5590; https://doi.org/10.3390/molecules25235590 - 27 Nov 2020

Cited by 4 | Viewed by 2180

Abstract

Karwinskia genus consists of shrubs and small trees. Four toxic compounds have been isolated from Karwinskia plants, which were typified as dimeric anthracenones and named T496, T514, T516, and T544. Moreover, several related compounds have been isolated and characterized. Here we review the [...] Read more.

Karwinskia genus consists of shrubs and small trees. Four toxic compounds have been isolated from Karwinskia plants, which were typified as dimeric anthracenones and named T496, T514, T516, and T544. Moreover, several related compounds have been isolated and characterized. Here we review the toxicity of the fruit of Karwinskia plants when ingested (accidentally or experimentally), as well as the toxicity of its isolated compounds. Additionally, we analyze the probable antineoplastic effect of T514. Toxins cause damage mainly to nervous system, liver, lung, and kidney. The pathophysiological mechanism has not been fully understood but includes metabolic and structural alterations that can lead cells to apoptosis or necrosis. T514 has shown selective toxicity in vitro against human cancer cells. T514 causes selective and irreversible damage to peroxisomes; for this reason, it was renamed peroxisomicine A1 (PA1). Since a significant number of malignant cell types contain fewer peroxisomes than normal cells, tumor cells would be more easily destroyed by PA1 than healthy cells. Inhibition of topoisomerase II has also been suggested to play a role in the effect of PA1 on malignant cells. More research is needed, but the evidence obtained so far indicates that PA1 could be an effective anticancer agent. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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40 pages, 5231 KiB

Open AccessReview

A Review of Cytotoxic Plants of the Indian Subcontinent and a Broad-Spectrum Analysis of Their Bioactive Compounds

by Kishor Mazumder, Biswajit Biswas, Iqbal Mahmud Raja and Koichi Fukase

Molecules 2020, 25(8), 1904; https://doi.org/10.3390/molecules25081904 - 20 Apr 2020

Cited by 27 | Viewed by 6662

Abstract

Cancer or uncontrolled cell proliferation is a major health issue worldwide and is the second leading cause of deaths globally. The high mortality rate and toxicity associated with cancer chemotherapy or radiation therapy have encouraged the investigation of complementary and alternative treatment methods, [...] Read more.

Cancer or uncontrolled cell proliferation is a major health issue worldwide and is the second leading cause of deaths globally. The high mortality rate and toxicity associated with cancer chemotherapy or radiation therapy have encouraged the investigation of complementary and alternative treatment methods, such as plant-based drugs. Moreover, over 60% of the anti-cancer drugs are molecules derived from plants or their synthetic derivatives. Therefore, in the present review, an attempt has been made to summarize the cytotoxic plants available in the Indian subcontinent along with a description of their bio-active components. The review covers 99 plants of 57 families as well as over 110 isolated bioactive cytotoxic compounds, amongst which at least 20 are new compounds. Among the reported phytoconstituents, artemisinin, lupeol, curcumin, and quercetin are under clinical trials, while brazilin, catechin, ursolic acid, β-sitosterol, and myricetin are under pharmacokinetic development. However, for the remaining compounds, there is little or no information available. Therefore, further investigations are warranted on these subcontinent medicinal plants as an important source of novel cytotoxic agents. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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