Research

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17 pages, 5142 KiB

Open AccessArticle

Quercetin Induces Apoptosis in HepG2 Cells via Directly Interacting with YY1 to Disrupt YY1-p53 Interaction

by Hui Guan, Wenyuan Zhang, Hui Liu, Yang Jiang, Feng Li, Maoyu Wu, Geoffrey I. N. Waterhouse, Dongxiao Sun-Waterhouse and Dapeng Li

Metabolites 2023, 13(2), 229; https://doi.org/10.3390/metabo13020229 - 03 Feb 2023

Cited by 8 | Viewed by 2148

Abstract

Quercetin is a flavonol found in edible plants and possesses a significant anticancer activity. This study explored the mechanism by which quercetin prevented liver cancer via inducing apoptosis in HepG2 cells. Quercetin induced cell proliferation and apoptosis through inhibiting YY1 and facilitating p53 [...] Read more.

Quercetin is a flavonol found in edible plants and possesses a significant anticancer activity. This study explored the mechanism by which quercetin prevented liver cancer via inducing apoptosis in HepG2 cells. Quercetin induced cell proliferation and apoptosis through inhibiting YY1 and facilitating p53 expression and subsequently increasing the Bax/Bcl-2 ratio. The results revealed that YY1 knockdown promoted apoptosis, whilst YY1 overexpression suppressed apoptosis via direct physical interaction between YY1 and p53 to regulate the p53 signaling pathway. Molecular docking using native and mutant YY1 proteins showed that quercetin could interact directly with YY1, and the binding of quercetin to YY1 significantly decreased the docking energy of YY1 with p53 protein. The interactions between quercetin and YY1 protein included direct binding and non-bonded indirect interactions, as confirmed by cellular thermal shift assay, UV-Vis absorption spectroscopy, fluorescence spectroscopy and circular dichroism spectroscopy. It was likely that quercetin directly bound to YY1 protein to compete with p53 for the binding sites of YY1 to disrupt the YY1-p53 interaction, thereby promoting p53 activation. This study provides insights into the mechanism underlying quercetin’s anticancer action and supports the development of quercetin as an anticancer therapeutic agent. Full article

(This article belongs to the Special Issue Effects of Plant Active Components on Cell Metabolism and Their Anti-tumor Properties)

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22 pages, 4419 KiB

Open AccessArticle

Natural Steroidal Lactone Induces G1/S Phase Cell Cycle Arrest and Intrinsic Apoptotic Pathway by Up-Regulating Tumor Suppressive miRNA in Triple-Negative Breast Cancer Cells

by Mohd Shuaib, Kumari Sunita Prajapati, Sanjay Gupta and Shashank Kumar

Metabolites 2023, 13(1), 29; https://doi.org/10.3390/metabo13010029 - 24 Dec 2022

Cited by 9 | Viewed by 1652

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with minimal treatment options. In the present work, Withaferin A (WA), a natural steroidal lactone found in Withania somnifera (Solanaceae), was studied to deduce the miRNA expression modulation mediated anticancer mode of [...] Read more.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with minimal treatment options. In the present work, Withaferin A (WA), a natural steroidal lactone found in Withania somnifera (Solanaceae), was studied to deduce the miRNA expression modulation mediated anticancer mode of action in TNBC cells. Small RNA next generation sequencing (NGS) of WA (2 µM) and vehicle (0.1% DMSO)-treated MDA-MB-231 cells revealed a total of 413 differentially expressed miRNAs (DEMs) and demonstrated that WA potentially up-regulates the miR-181c-5p, miR-15a-5p, miR-500b-5p, miR-191-3p, and miR-34a-5p and down-regulates miR-1275, miR-326, miR-1908-5p, and miR-3940-3p among total DEMs. The NGS and qRT-PCR expression analysis revealed a significantly higher expression of miR-181c-5p among the top 10 DEMs. Predicted target genes of the DEMs showed enrichment in cancer-associated gene ontology terms and KEGG signaling pathways. Transient up-expression of mir-181c-5p showed a time-dependent decrease in MDA-MB-231 and MDA-MB-453 cell viability. Co-treatment of miR-181c-5p mimic and WA (at varying concentration) down-regulated cell cycle progression markers (CDK4 and Cyclin D1) at mRNA and protein levels. The treatment induced apoptosis in MDA-MB-231 cells by modulating the expression/activity of Bax, Bcl2, Caspase 3, Caspase 8, Caspase 3/7, and PARP at mRNA and protein levels. Confocal microscopy and Annexin PI assays revealed apoptotic induction in miRNA- and steroidal-lactone-treated MDA-MB-231 cells. Results indicate that the Withaferin A and miRNA mimic co-treatment strategy may be utilized as a newer therapeutic strategy to treat triple-negative breast cancer. Full article

(This article belongs to the Special Issue Effects of Plant Active Components on Cell Metabolism and Their Anti-tumor Properties)

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13 pages, 13306 KiB

Open AccessArticle

The Metabolomic Profile of the Essential Oil from Zanthoxylum caribaeum (syn. chiloperone) Growing in Guadeloupe FWI using GC × GC-TOFMS

by Lea Farouil, Ryan P. Dias, Gianni Popotte-Julisson, Garrick Bibian, Ahissan Innocent Adou, A. Paulina de la Mata, Muriel Sylvestre, James J. Harynuk and Gerardo Cebrián-Torrejón

Metabolites 2022, 12(12), 1293; https://doi.org/10.3390/metabo12121293 - 19 Dec 2022

Cited by 2 | Viewed by 1525

Abstract

The essential oil (EO) from the leaves of Zanthoxylum caribaeum (syn. Chiloperone) (Rutaceae) was studied previously for its acaricidal, antimicrobial, antioxidant, and insecticidal properties. In prior studies, the most abundant compound class found in leaf oils from Brazil, Costa Rica, and Paraguay [...] Read more.

The essential oil (EO) from the leaves of Zanthoxylum caribaeum (syn. Chiloperone) (Rutaceae) was studied previously for its acaricidal, antimicrobial, antioxidant, and insecticidal properties. In prior studies, the most abundant compound class found in leaf oils from Brazil, Costa Rica, and Paraguay was terpenoids. Herein, essential oil from the leaves of Zanthoxylum caribaeum (prickly yellow, bois chandelle blanc (FWI), peñas Blancas (Costa Rica), and tembetary hu (Paraguay)) growing in Guadeloupe was analyzed with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC-TOFMS), and thirty molecules were identified. A comparison with previously published leaf EO compositions of the same species growing in Brazil, Costa Rica, and Paraguay revealed a number of molecules in common such as β-myrcene, limonene, β-caryophyllene, α-humulene, and spathulenol. Some molecules identified in Zanthoxylum caribaeum from Guadeloupe showed some antimetabolic effects on enzymes; the in-depth study of this plant and its essential oil with regard to metabolic diseases merits further exploration. Full article

(This article belongs to the Special Issue Effects of Plant Active Components on Cell Metabolism and Their Anti-tumor Properties)

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18 pages, 3799 KiB

Open AccessArticle

Rutin Potentially Binds the Gamma Secretase Catalytic Site, Down Regulates the Notch Signaling Pathway and Reduces Sphere Formation in Colonospheres

by Atul Kumar Singh, Mohd Shuaib, Kumari Sunita Prajapati and Shashank Kumar

Metabolites 2022, 12(10), 926; https://doi.org/10.3390/metabo12100926 - 29 Sep 2022

Cited by 8 | Viewed by 2013

Abstract

Rutin, a natural flavonol, can modulate molecular signaling pathways and has considerable potential in cancer treatment. However, little is known about the effect of rutin on the notch signaling pathway (NSP) in cancer and cancer stem-like cells. In this study, we explored the [...] Read more.

Rutin, a natural flavonol, can modulate molecular signaling pathways and has considerable potential in cancer treatment. However, little is known about the effect of rutin on the notch signaling pathway (NSP) in cancer and cancer stem-like cells. In this study, we explored the effect of rutin on gamma secretase (GS, a putative notch signaling target) inhibition mediated NICD (Notch Intracellular Domain) production in colon cancer cells. Molecular docking, MM-GBSA, and Molecular dynamics (MD) simulation experiments were performed to check rutin’s GS catalytic site binding potential. The HCT-116 colon cancer and cancer stem-like cells (colonospheres) were utilized to validate the in silico findings. The NICD production, notch promoter assay, expression of notch target genes, and cancer stemness/self-renewal markers were studied at molecular levels. The results were compared with the Notch-1 siRNA transfected test cells. The in silico study revealed GS catalytic site binding potential in rutin. The in vitro results showed a decreased NICD formation, an altered notch target gene (E-cad, Hes-1, and Hey-1) expression, and a reduction in stemness/self-renewal markers (CD44, c-Myc, Nanog, and Sox2) in test cells in a time and dose-dependent manner. In conclusion, rutin inhibits the notch signaling pathway and reduces the stemness/self-renewal property in colon cancer cells and the colonospheres by targeting gamma secretase. The clinical efficacy of rutin in combination therapy in colon cancer may be studied in the future. Full article

(This article belongs to the Special Issue Effects of Plant Active Components on Cell Metabolism and Their Anti-tumor Properties)

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25 pages, 23342 KiB

Open AccessArticle

Elemental Analysis, Phytochemical Screening and Evaluation of Antioxidant, Antibacterial and Anticancer Activity of Pleurotus ostreatus through In Vitro and In Silico Approaches

by Vartika Mishra, Sarika Tomar, Priyanka Yadav, Shraddha Vishwakarma and Mohan Prasad Singh

Metabolites 2022, 12(9), 821; https://doi.org/10.3390/metabo12090821 - 31 Aug 2022

Cited by 11 | Viewed by 2567

Abstract

Oyster mushrooms form an integral part of many diets owing to their characteristic aroma, delicious taste and nutraceutical value. In this study, we examined oyster mushrooms by direct arc optical emission spectroscopy for the presence of various biologically important elements. Furthermore, we screened [...] Read more.

Oyster mushrooms form an integral part of many diets owing to their characteristic aroma, delicious taste and nutraceutical value. In this study, we examined oyster mushrooms by direct arc optical emission spectroscopy for the presence of various biologically important elements. Furthermore, we screened phytochemicals present in Pleurotus ostreatus by applying GC-MS. Additionally, the antioxidant, antibacterial and anticancer activities of the ethanolic extract of Pleurotus ostreatus were studied. Moreover, we docked the phytochemicals and examined their binding affinities with EGFR, PR and NF-κB proteins, which are overexpressed in breast cancer. The elemental analysis showed the presence of Fe, K, Na, Ca, Mg, Cr and Sr in the spectrum. Moreover, GC-MS data revealed the presence of 32 biologically active compounds in oyster mushrooms. The ethanolic extract displayed remarkable free radical scavenging activity (~50%) against DPPH. The mushroom has shown promising antibacterial activity against both Gram-positive (S. aureus) and Gram-negative bacteria (Pseudomonasaeruginosa, Proteus vulgaris and Proteus mirabilis). The present study also revealed that oyster mushrooms possess significant anticancer activity. The ethanolic extract inhibited the growth and proliferation of MCF-7 cells. It also induced cell shrinkage, membrane blebbing and nuclear fragmentation, resulting in apoptosis of malignant cells. The molecular docking analysis showed that ligand 15 (Linoleic acid ethyl ester), ligand 27 (Ergosta-5,7,9(11),22-tetraen-3-ol, (3. beta.,22E), ligand 28 (Stigmasta-5,22-dien-3-ol, acetate, (3. beta.,22Z), ligand 30 (Ergosta-5,7,22-Trien-3-Ol, (3. Beta.,22E) and ligand 32 (gamma. Sitosterol) exhibited better binding affinities with EGFR, PR and NF-κB proteins. This result provides a strong ground for confirmation of the in vitro anticancer effect of Pleurotus ostreatus. From the present in vitro and in silico studies, it can be concluded that Pleurotus ostreatus is a useful source of essential elements and reservoir of bioactive compounds which confer its significant antioxidant, antibacterial and anticancer properties. Full article

(This article belongs to the Special Issue Effects of Plant Active Components on Cell Metabolism and Their Anti-tumor Properties)

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Review

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19 pages, 2275 KiB

Open AccessReview

Anticancer Potential of Apigenin and Isovitexin with Focus on Oncogenic Metabolism in Cancer Stem Cells

by Maryam Ghanbari-Movahed, Sahar Shafiee, Jack T. Burcher, Ricardo Lagoa, Mohammad Hosein Farzaei and Anupam Bishayee

Metabolites 2023, 13(3), 404; https://doi.org/10.3390/metabo13030404 - 09 Mar 2023

Cited by 7 | Viewed by 2439

Abstract

It has been demonstrated that cancer stem cells (CSCs) go through metabolic changes that differentiate them from non-CSCs. The altered metabolism of CSCs plays a vital role in tumor initiation, progression, immunosuppression, and resistance to conventional therapy. Therefore, defining the role of CSC [...] Read more.

It has been demonstrated that cancer stem cells (CSCs) go through metabolic changes that differentiate them from non-CSCs. The altered metabolism of CSCs plays a vital role in tumor initiation, progression, immunosuppression, and resistance to conventional therapy. Therefore, defining the role of CSC metabolism in carcinogenesis has emerged as a main focus in cancer research. Two natural flavonoids, apigenin and isovitexin, have been shown to act synergistically with conventional chemotherapeutic drugs by sensitizing CSCs, ultimately leading to improved therapeutic efficacy. The aim of this study is to present a critical and broad evaluation of the anti-CSC capability of apigenin and isovitexin in different cancers as novel and untapped natural compounds for developing drugs. A thorough review of the included literature supports a strong association between anti-CSC activity and treatment with apigenin or isovitexin. Additionally, it has been shown that apigenin or isovitexin affected CSC metabolism and reduced CSCs through various mechanisms, including the suppression of the Wnt/β-catenin signaling pathway, the inhibition of nuclear factor-κB protein expression, and the downregulation of the cell cycle via upregulation of p21 and cyclin-dependent kinases. The findings of this study demonstrate that apigenin and isovitexin are potent candidates for treating cancer due to their antagonistic effects on CSC metabolism. Full article

(This article belongs to the Special Issue Effects of Plant Active Components on Cell Metabolism and Their Anti-tumor Properties)

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28 pages, 2704 KiB

Open AccessReview

Inhibiting Angiogenesis by Anti-Cancer Saponins: From Phytochemistry to Cellular Signaling Pathways

by Mohammad Bagher Majnooni, Sajad Fakhri, Syed Mustafa Ghanadian, Gholamreza Bahrami, Kamran Mansouri, Amin Iranpanah, Mohammad Hosein Farzaei and Mahdi Mojarrab

Metabolites 2023, 13(3), 323; https://doi.org/10.3390/metabo13030323 - 22 Feb 2023

Cited by 7 | Viewed by 2604

Abstract

Saponins are one of the broadest classes of high-molecular-weight natural compounds, consisting mainly of a non-polar moiety with 27 to 30 carbons and a polar moiety containing sugars attached to the sapogenin structure. Saponins are found in more than 100 plant families as [...] Read more.

Saponins are one of the broadest classes of high-molecular-weight natural compounds, consisting mainly of a non-polar moiety with 27 to 30 carbons and a polar moiety containing sugars attached to the sapogenin structure. Saponins are found in more than 100 plant families as well as found in marine organisms. Saponins have several therapeutic effects, including their administration in the treatment of various cancers. These compounds also reveal noteworthy anti-angiogenesis effects as one of the critical strategies for inhibiting cancer growth and metastasis. In this study, a comprehensive review is performed on electronic databases, including PubMed, Scopus, ScienceDirect, and ProQuest. Accordingly, the structural characteristics of triterpenoid/steroid saponins and their anti-cancer effects were highlighted, focusing on their anti-angiogenic effects and related mechanisms. Consequently, the anti-angiogenic effects of saponins, inhibiting the expression of genes related to vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF-1α) are two main anti-angiogenic mechanisms of triterpenoid and steroidal saponins. The inhibition of inflammatory signaling pathways that stimulate angiogenesis, such as pro-inflammatory cytokines, mitogen-activated protein kinase (MAPKs), and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt), are other anti-angiogenic mechanisms of saponins. Furthermore, the anti-angiogenic and anti-cancer activity of saponins was closely related to the binding site of the sugar moiety, the type and number of their monosaccharide units, as well as the presence of some functional groups in their aglycone structure. Therefore, saponins are suitable candidates for cancer treatment by inhibiting angiogenesis, for which extensive pre-clinical and comprehensive clinical trial studies are recommended. Full article

(This article belongs to the Special Issue Effects of Plant Active Components on Cell Metabolism and Their Anti-tumor Properties)

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27 pages, 3207 KiB

Open AccessReview

Natural Products Targeting Hsp90 for a Concurrent Strategy in Glioblastoma and Neurodegeneration

by Sarmistha Mitra, Raju Dash, Yeasmin Akter Munni, Nusrat Jahan Selsi, Nasrin Akter, Md Nazim Uddin, Kishor Mazumder and Il Soo Moon

Metabolites 2022, 12(11), 1153; https://doi.org/10.3390/metabo12111153 - 21 Nov 2022

Cited by 2 | Viewed by 2625

Abstract

Glioblastoma multiforme (GBM) is one of the most common aggressive, resistant, and invasive primary brain tumors that share neurodegenerative actions, resembling many neurodegenerative diseases. Although multiple conventional approaches, including chemoradiation, are more frequent in GBM therapy, these approaches are ineffective in extending the [...] Read more.

Glioblastoma multiforme (GBM) is one of the most common aggressive, resistant, and invasive primary brain tumors that share neurodegenerative actions, resembling many neurodegenerative diseases. Although multiple conventional approaches, including chemoradiation, are more frequent in GBM therapy, these approaches are ineffective in extending the mean survival rate and are associated with various side effects, including neurodegeneration. This review proposes an alternative strategy for managing GBM and neurodegeneration by targeting heat shock protein 90 (Hsp90). Hsp90 is a well-known molecular chaperone that plays essential roles in maintaining and stabilizing protein folding to degradation in protein homeostasis and modulates signaling in cancer and neurodegeneration by regulating many client protein substrates. The therapeutic benefits of Hsp90 inhibition are well-known for several malignancies, and recent evidence highlights that Hsp90 inhibitors potentially inhibit the aggressiveness of GBM, increasing the sensitivity of conventional treatment and providing neuroprotection in various neurodegenerative diseases. Herein, the overview of Hsp90 modulation in GBM and neurodegeneration progress has been discussed with a summary of recent outcomes on Hsp90 inhibition in various GBM models and neurodegeneration. Particular emphasis is also given to natural Hsp90 inhibitors that have been evidenced to show dual protection in both GBM and neurodegeneration. Full article

(This article belongs to the Special Issue Effects of Plant Active Components on Cell Metabolism and Their Anti-tumor Properties)

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31 pages, 1484 KiB

Open AccessReview

Recent Advances in Glycyrrhiza glabra (Licorice)-Containing Herbs Alleviating Radiotherapy- and Chemotherapy-Induced Adverse Reactions in Cancer Treatment

by Kai-Lee Wang, Ying-Chun Yu, Hsin-Yuan Chen, Yi-Fen Chiang, Mohamed Ali, Tzong-Ming Shieh and Shih-Min Hsia

Metabolites 2022, 12(6), 535; https://doi.org/10.3390/metabo12060535 - 09 Jun 2022

Cited by 11 | Viewed by 3512

Abstract

Cancers represent a significant cause of morbidity and mortality worldwide. They also impose a large economic burden on patients, their families, and health insurance systems. Notably, cancers and the adverse reactions to their therapeutic options, chemotherapy and radiotherapy, dramatically affect the quality of [...] Read more.

Cancers represent a significant cause of morbidity and mortality worldwide. They also impose a large economic burden on patients, their families, and health insurance systems. Notably, cancers and the adverse reactions to their therapeutic options, chemotherapy and radiotherapy, dramatically affect the quality of life of afflicted patients. Therefore, developing approaches to manage chemotherapy- and radiotherapy-induced adverse reactions gained greater attention in recent years. Glycyrrhiza glabra (licorice), a perennial plant that is one of the most frequently used herbs in traditional Chinese medicine, has been heavily investigated in relation to cancer therapy. Licorice/licorice-related regimes, used in combination with chemotherapy, may improve the adverse effects of chemotherapy. However, there is little awareness of licorice-containing herbs alleviating reactions to radiotherapy and chemotherapy, or to other induced adverse reactions in cancer treatment. We aimed to provide a descriptive review, and to emphasize the possibility that licorice-related medicines could be used as an adjuvant regimen with chemotherapy to improve quality of life (QoL) and to reduce side effects, thus, improving compliance with chemotherapy. The experimental method involved searching different databases, including PubMed, the Cochrane Library, and Wang Fang database, as of May 2022, to identify any relevant studies. Despite a lack of high-quality and large-scale randomized controlled trials, we still discovered the potential benefits of licorice-containing herbs from published clinical studies. These studies find that licorice-containing herbs, and their active ingredients, reduce the adverse reactions caused by chemotherapy and radiotherapy, and improve the QoL of patients. This comprehensive review will serve as a cornerstone to encourage more scientists to evaluate and develop effective Traditional Chinese medicine prescriptions to improve the side effects of chemotherapy and radiation therapy. Full article

(This article belongs to the Special Issue Effects of Plant Active Components on Cell Metabolism and Their Anti-tumor Properties)

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