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19 pages, 5443 KiB

Open AccessArticle

Ponciri Fructus Immatarus Sensitizes the Apoptotic Effect of Hyperthermia Treatment in AGS Gastric Cancer Cells through ROS-Dependent HSP Suppression

by Chae Ryeong Ahn, Hyo In Kim, Jai-Eun Kim, In Jin Ha, Kwang Seok Ahn, Jinbong Park, Young Woo Kim and Seung Ho Baek

Biomedicines 2023, 11(2), 405; https://doi.org/10.3390/biomedicines11020405 - 30 Jan 2023

Cited by 3 | Viewed by 1626

Abstract

Gastric cancer has been associated with a high incidence and mortality, accompanied by a poor prognosis. Given the limited therapeutic options to treat gastric cancer, alternative treatments need to be urgently developed. Hyperthermia therapy is a potentially effective and safe treatment option for [...] Read more.

Gastric cancer has been associated with a high incidence and mortality, accompanied by a poor prognosis. Given the limited therapeutic options to treat gastric cancer, alternative treatments need to be urgently developed. Hyperthermia therapy is a potentially effective and safe treatment option for cancer; however, certain limitations need to be addressed. We applied 43 °C hyperthermia to AGS gastric cancer cells combined with Ponciri Fructus Immaturus (PF) to establish their synergistic effects. Co-treatment with PF and hyperthermia synergistically suppressed AGS cell proliferation by inducing extrinsic and intrinsic apoptotic pathways. Additionally, PF and hyperthermia suppressed factors related to metastasis. Cell cycle arrest was determined by flow cytometry, revealing that co-treatment induced arrest at the G2/M phase. As reactive oxygen species (ROS) are critical in hyperthermia therapy, we next examined changes in ROS generation. Co-treatment with PF and hyperthermia increased ROS levels, and apoptotic induction mediated by this combination was partially dependent on ROS generation. Furthermore, heat shock factor 1 and heat shock proteins (HSPs) were notably suppressed following co-treatment with PF and hyperthermia. The HSP-regulating effect was also dependent on ROS generation. Overall, these findings suggest that co-treatment with PF and hyperthermia could afford a promising anticancer therapy for gastric cancer. Full article

(This article belongs to the Special Issue Anticancer Activity and Metabolic Pathways of Natural Products)

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21 pages, 3363 KiB

Open AccessArticle

Husk-like Zinc Oxide Nanoparticles Induce Apoptosis through ROS Generation in Epidermoid Carcinoma Cells: Effect of Incubation Period on Sol-Gel Synthesis and Anti-Cancerous Properties

by Wardah A. Alhoqail, Abdulaziz S. Alothaim, Mohd Suhail, Danish Iqbal, Mehnaz Kamal, Majid Mohammed Asmari and Azfar Jamal

Biomedicines 2023, 11(2), 320; https://doi.org/10.3390/biomedicines11020320 - 23 Jan 2023

Cited by 8 | Viewed by 2001

Abstract

This study effectively reports the influence of experimental incubation period on the sol-gel production of husk-like zinc oxide nanoparticles (ZNPs) and their anti-cancerous abilities. The surface morphology of ZNPs was studied with the help of SEM. With the use of TEM, the diameter [...] Read more.

This study effectively reports the influence of experimental incubation period on the sol-gel production of husk-like zinc oxide nanoparticles (ZNPs) and their anti-cancerous abilities. The surface morphology of ZNPs was studied with the help of SEM. With the use of TEM, the diameter range of the ZNPs was estimated to be ~86 and ~231 nm for ZNP^A and ZNP^B, prepared by incubating zinc oxide for 2 and 10 weeks, respectively. The X-ray diffraction (XRD) investigation showed that ZNPs had a pure wurtzite crystal structure. On prolonging the experimental incubation, a relative drop in aspect ratio was observed, displaying a distinct blue-shift in the UV-visible spectrum. Furthermore, RBC lysis assay results concluded that ZNP^A and ZNP^B both demonstrated innoxious nature. As indicated by MTT assay, reactive oxygen species (ROS) release, and chromatin condensation investigations against the human epidermoid carcinoma (HEC) A431 cells, ZNP^B demonstrated viable relevance to chemotherapy. Compared to ZNP^B, ZNP^A had a slightly lower IC₅₀ against A431 cells due to its small size. This study conclusively describes a simple, affordable method to produce ZNP nano-formulations that display significant cytotoxicity against the skin cancer cell line A431, suggesting that ZNPs may be useful in the treatment of cancer. Full article

(This article belongs to the Special Issue Anticancer Activity and Metabolic Pathways of Natural Products)

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17 pages, 4354 KiB

Open AccessArticle

Chemopreventive Effects of Oral Pterostilbene in Multistage Carcinogenesis of Skin Squamous Cell Carcinoma Mouse Model Induced by DMBA/TPA

by Omchit Surien, Siti Fathiah Masre, Dayang Fredalina Basri and Ahmad Rohi Ghazali

Biomedicines 2022, 10(11), 2743; https://doi.org/10.3390/biomedicines10112743 - 28 Oct 2022

Cited by 7 | Viewed by 1949

Abstract

Skin squamous cell carcinoma (SCC) is a type of non-melanoma skin cancer. Pterostilbene is a natural compound proven to exhibit various pharmacological properties, including chemo-preventive effects. This study aimed to explore the chemo-preventive effect of oral pterostilbene during initiation, promotion or continuous on [...] Read more.

Skin squamous cell carcinoma (SCC) is a type of non-melanoma skin cancer. Pterostilbene is a natural compound proven to exhibit various pharmacological properties, including chemo-preventive effects. This study aimed to explore the chemo-preventive effect of oral pterostilbene during initiation, promotion or continuous on multistage skin SCC mouse models induced by 7,12-Dimethylbenz(a)anthracene (DMBA)/12-O-Tetradecanoylphorbol-13-acetate (TPA). The experimental design consists of five groups of female Institute of Cancer Research (ICR) mice, with two control groups of vehicle and cancer. Three oral pterostilbene groups consisted of orally administered pterostilbene during initiation, promotion, or continuously. Oral pterostilbene significantly reduced the number and volume of tumours. Oral pterostilbene demonstrated less severe skin histology changes compared to the cancer control group, with less pleomorphic in the cells and nuclei, and the basement membrane remained intact. Our results showed fewer invasive tumours in oral PT-treated groups than in cancer groups that displayed mitotic bodies, highly pleomorphic cells and nuclei, and basement membrane invasion. The cell proliferation marker (Ki-67) was reduced in oral pterostilbene-treated groups. Overall, oral pterostilbene is a promising chemo-preventive intervention due to its anti-initiation and anti-promotion on skin carcinogenesis. Thus, the potential molecular mechanisms of oral pterostilbene chemo-prevention agent should be explored. Full article

(This article belongs to the Special Issue Anticancer Activity and Metabolic Pathways of Natural Products)

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14 pages, 3389 KiB

Open AccessArticle

Sanguinarine Induces H₂O₂-Dependent Apoptosis and Ferroptosis in Human Cervical Cancer

by Ameer Alakkal, Faisal Thayyullathil, Siraj Pallichankandy, Karthikeyan Subburayan, Anees Rahman Cheratta and Sehamuddin Galadari

Biomedicines 2022, 10(8), 1795; https://doi.org/10.3390/biomedicines10081795 - 26 Jul 2022

Cited by 12 | Viewed by 3277

Abstract

Sanguinarine (SNG) is a benzophenanthridine alkaloid isolated mainly from Sanguinaria canadensis, Chelidonium majus, and Macleaya cordata. SNG is considered an antineoplastic agent based on its cytotoxic activity against various tumors. However, the exact molecular mechanism through which SNG mediates this [...] Read more.

Sanguinarine (SNG) is a benzophenanthridine alkaloid isolated mainly from Sanguinaria canadensis, Chelidonium majus, and Macleaya cordata. SNG is considered an antineoplastic agent based on its cytotoxic activity against various tumors. However, the exact molecular mechanism through which SNG mediates this activity has not been elucidated. Here, we report that SNG induces death in human cervical cancer (HeLa) cells through activation of two interdependent cell death pathways—apoptosis and ferroptosis. SNG-induced apoptosis was characterized by caspase activation and PARP cleavage, while ferroptosis involved solute carrier family 7 member 11 (SLC7A11) down-regulation, glutathione (GSH) depletion, iron accumulation, and lipid peroxidation (LPO). Interestingly, incubation with caspase inhibitor z-VAD-fmk not only inhibited the features of apoptosis, but also negated markers of SNG-induced ferroptosis. Similarly, pretreatment with ferroptosis inhibitor ferrostatin-1 (Fer-1), apart from rescuing cells from SNG-induced ferroptosis, also curbed the features of SNG-induced apoptosis. Our study implies that, together, apoptosis and ferroptosis act as partners in the context of SNG mediated tumor suppression in HeLa cells. Importantly, SNG increased the generation of reactive oxygen species (ROS), and ROS inhibition blocks the induction of both apoptosis and ferroptosis. These findings highlight the value of continued investigation into the potential use of SNG as an antineoplastic agent. Full article

(This article belongs to the Special Issue Anticancer Activity and Metabolic Pathways of Natural Products)

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14 pages, 3057 KiB

Open AccessArticle

CDI Exerts Anti-Tumor Effects by Blocking the FoxM1-DNA Interaction

by Woo Dae Jang, Mi Young Lee, Jihye Mun, Gyutae Lim and Kwang-Seok Oh

Biomedicines 2022, 10(7), 1671; https://doi.org/10.3390/biomedicines10071671 - 11 Jul 2022

Cited by 4 | Viewed by 1660

Abstract

The Forkhead box protein M1 (FoxM1) is an appealing target for anti-cancer therapeutics as this cell proliferation-associated transcription factor is overexpressed in most human cancers. FoxM1 is involved in tumor invasion, angiogenesis, and metastasis. To discover novel inhibitors that disrupt the FoxM1-DNA interaction, [...] Read more.

The Forkhead box protein M1 (FoxM1) is an appealing target for anti-cancer therapeutics as this cell proliferation-associated transcription factor is overexpressed in most human cancers. FoxM1 is involved in tumor invasion, angiogenesis, and metastasis. To discover novel inhibitors that disrupt the FoxM1-DNA interaction, we identified CDI, a small molecule that inhibits the FoxM1–DNA interaction. CDI was identified through an assay based on the time-resolved fluorescence energy transfer response of a labeled consensus oligonucleotide that was bound to a recombinant FoxM1-dsDNA binding domain (FoxM1-DBD) protein and exhibited potent inhibitory activity against FoxM1-DNA interaction. CDI suppressed cell proliferation and induced apoptosis in MDA-MB-231 cells obtained from a breast cancer patient. Furthermore, it decreased not only the mRNA and protein expression of FoxM1 but also that of downstream targets such as CDC25b. Additionally, global transcript profiling of MDA-MB-231 cells by RNA-Seq showed that CDI decreases the expression of FoxM1-regulated genes. The docking and MD simulation results indicated that CDI likely binds to the DNA interaction site of FoxM1-DBD and inhibits the function of FoxM1-DBD. These results of CDI being a possible effective inhibitor of FoxM1-DNA interaction will encourage its usage in pharmaceutical applications. Full article

(This article belongs to the Special Issue Anticancer Activity and Metabolic Pathways of Natural Products)

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15 pages, 5002 KiB

Open AccessArticle

Kinetin Ameliorates Cisplatin-Induced Hepatotoxicity and Lymphotoxicity via Attenuating Oxidative Damage, Cell Apoptosis and Inflammation in Rats

by Moustafa Fathy, Mostafa A. Darwish, Al-Shaimaa M. Abdelhamid, Gehad M. Alrashedy, Othman Ali Othman, Muhammad Naseem, Thomas Dandekar and Eman M. Othman

Biomedicines 2022, 10(7), 1620; https://doi.org/10.3390/biomedicines10071620 - 06 Jul 2022

Cited by 5 | Viewed by 1874

Abstract

Though several previous studies reported the in vitro and in vivo antioxidant effect of kinetin (Kn), details on its action in cisplatin-induced toxicity are still scarce. In this study we evaluated, for the first time, the effects of kinetin in cisplatin (cp)- induced [...] Read more.

Though several previous studies reported the in vitro and in vivo antioxidant effect of kinetin (Kn), details on its action in cisplatin-induced toxicity are still scarce. In this study we evaluated, for the first time, the effects of kinetin in cisplatin (cp)- induced liver and lymphocyte toxicity in rats. Wistar male albino rats were divided into nine groups: (i) the control (C), (ii) groups 2,3 and 4, which received 0.25, 0.5 and 1 mg/kg kinetin for 10 days; (iii) the cisplatin (cp) group, which received a single intraperitoneal injection of CP (7.0 mg/kg); and (iv) groups 6, 7, 8 and 9, which received, for 10 days, 0.25, 0.5 and 1 mg/kg kinetin or 200 mg/kg vitamin C, respectively, and Cp on the fourth day. CP-injected rats showed a significant impairment in biochemical, oxidative stress and inflammatory parameters in hepatic tissue and lymphocytes. PCR showed a profound increase in caspase-3, and a significant decline in AKT gene expression. Intriguingly, Kn treatment restored the biochemical, redox status and inflammatory parameters. Hepatic AKT and caspase-3 expression as well as CD95 levels in lymphocytes were also restored. In conclusion, Kn mitigated oxidative imbalance, inflammation and apoptosis in CP-induced liver and lymphocyte toxicity; therefore, it can be considered as a promising therapy. Full article

(This article belongs to the Special Issue Anticancer Activity and Metabolic Pathways of Natural Products)

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14 pages, 2846 KiB

Open AccessArticle

Disruption of Colorectal Cancer Network by Polyphyllins Reveals Pivotal Entities with Implications for Chemoimmunotherapy

by Ram Siripuram, Zinka Bartolek, Ketki Patil, Saj S. Gill and S. Balakrishna Pai

Biomedicines 2022, 10(3), 583; https://doi.org/10.3390/biomedicines10030583 - 02 Mar 2022

Cited by 4 | Viewed by 2194

Abstract

The prevalence of colorectal cancer has increased world-wide with high rates of mortality and morbidity. In the absence of efficacious drugs to treat this neoplasia, there is an imminent need to discover molecules with multifaceted effects. To this end, we opted to study [...] Read more.

The prevalence of colorectal cancer has increased world-wide with high rates of mortality and morbidity. In the absence of efficacious drugs to treat this neoplasia, there is an imminent need to discover molecules with multifaceted effects. To this end, we opted to study the effect of steroidal saponins such as Polyphyllins. We performed anticancer activity studies with three analogs of Polyphyllins: Polyphyllin D (PD), Polyphyllin II (PII) and Polyphyllin G (PG). Here we show the potent effect of PD, PII (IC₅₀ of 0.5−1 µM) and PG (IC₅₀of 3 µM) in inhibiting the viability of colorectal adenocarcinoma cells (DLD-1) and colorectal carcinoma cells (HCT116). PD and PII also showed inhibition of cell proliferation and sustained response upon withdrawal of the compounds when assessed by clonogenic assays in both the cell lines. Elucidation of the molecular mode of action revealed impact on the programmed cell death pathway. Additionally, proteomic profiling of DLD-1 revealed pivotal proteins differentially regulated by PD and PII, including a downregulated peroxiredoxin-1 which is considered as one of the novel targets to combat colorectal cancers and an upregulated elongation factor 2 (EF2), one of the key molecules considered as a tumor associated antigen (TAA) in colon cancer. Entities of cell metabolic pathways including downregulation of the key enzyme Phosphoglycerate kinase 1 of the glycolytic pathway was also observed. Importantly, the fold changes per se of the key components has led to the loss of viability of the colorectal cancer cells. We envision that the multifaceted function of PD and PII against the proliferation of colorectal carcinoma cells could have potential for novel treatments such as chemoimmunotherapy for colorectal adenocarcinomas. Future studies to develop these compounds as potent anti-colorectal cancer agents are warranted. Full article

(This article belongs to the Special Issue Anticancer Activity and Metabolic Pathways of Natural Products)

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Review

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36 pages, 1291 KiB

Open AccessReview

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

by Francesco Gervasi and Fanny Pojero

Biomedicines 2024, 12(3), 502; https://doi.org/10.3390/biomedicines12030502 - 23 Feb 2024

Viewed by 1329

Abstract

The fact that the Mediterranean diet could represent a source of natural compounds with cancer-preventive and therapeutic activity has been the object of great interest, especially with regard to the mechanisms of action of polyphenols found in olive oil and olive leaves. Secoiridoid [...] Read more.

The fact that the Mediterranean diet could represent a source of natural compounds with cancer-preventive and therapeutic activity has been the object of great interest, especially with regard to the mechanisms of action of polyphenols found in olive oil and olive leaves. Secoiridoid oleuropein (OLE) and its derivative hydroxytyrosol (3,4-dihydroxyphenylethanol, HT) have demonstrated anti-proliferative properties against a variety of tumors and hematological malignancies both in vivo and in vitro, with measurable effects on cellular redox status, metabolism, and transcriptional activity. With this review, we aim to summarize the most up-to-date information on the potential use of OLE and HT for cancer treatment, making important considerations about OLE and HT bioavailability, OLE- and HT-mediated effects on drug metabolism, and OLE and HT dual activity as both pro- and antioxidants, likely hampering their use in clinical routine. Also, we focus on the details available on the effects of nutritionally relevant concentrations of OLE and HT on cell viability, redox homeostasis, and inflammation in order to evaluate if both compounds could be considered cancer-preventive agents or new potential chemotherapy drugs whenever their only source is represented by diet. Full article

(This article belongs to the Special Issue Anticancer Activity and Metabolic Pathways of Natural Products)

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16 pages, 1601 KiB

Open AccessReview

Role of Hyaluronic Acid in Selected Malignant Neoplasms in Women

by Anna Markowska, Michał Antoszczak, Janina Markowska and Adam Huczyński

Biomedicines 2023, 11(2), 304; https://doi.org/10.3390/biomedicines11020304 - 21 Jan 2023

Cited by 3 | Viewed by 2243

Abstract

Hyaluronic acid (HA) is a significant glycosaminoglycan component of the extracellular matrix, playing an essential role in cell localization and proliferation. However, high levels of HA may also correlate with multidrug resistance of tumor cells, an increased tendency to metastasize, or cancer progression, [...] Read more.

Hyaluronic acid (HA) is a significant glycosaminoglycan component of the extracellular matrix, playing an essential role in cell localization and proliferation. However, high levels of HA may also correlate with multidrug resistance of tumor cells, an increased tendency to metastasize, or cancer progression, and thus represent a very unfavorable prognosis for cancer patients. The purpose of this review article is to summarize the results of studies describing the relationship between HA, the main ligand of the CD44 receptor, or other components of the HA signaling pathway. In addition, we review the course of selected female malignancies, i.e., breast, cervical, endometrial, and ovarian cancer, with the main focus on the mechanisms oriented to CD44. We also analyze reports on the beneficial use of HA-containing preparations in adjuvant therapy among patients with these types of cancer. Data from the literature suggest that HA and its family members may be critical prognostic biomarkers of selected malignancies among women. Nevertheless, the results of the available studies are inconclusive, and the actual clinical significance of HA expression analysis is still quite enigmatic. In our opinion, the HA-CD44 signaling pathway should be an attractive target for future research related to targeted therapy in gynecological cancers. Full article

(This article belongs to the Special Issue Anticancer Activity and Metabolic Pathways of Natural Products)

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11 pages, 8866 KiB

Open AccessReview

Polysaccharide-Peptide from Trametes versicolor: The Potential Medicine for Colorectal Cancer Treatment

by Zhicheng He, Jian Lin, Yingying He and Shubai Liu

Biomedicines 2022, 10(11), 2841; https://doi.org/10.3390/biomedicines10112841 - 07 Nov 2022

Cited by 7 | Viewed by 3912

Abstract

The incidence and mortality of colorectal cancer have shown an upward trend in the past decade. Therefore, the prevention, diagnosis, and treatment of colorectal cancer still need our continuous attention. Finding compounds with strong anticancer activity and low toxicity is a good strategy [...] Read more.

The incidence and mortality of colorectal cancer have shown an upward trend in the past decade. Therefore, the prevention, diagnosis, and treatment of colorectal cancer still need our continuous attention. Finding compounds with strong anticancer activity and low toxicity is a good strategy for colorectal cancer (CRC) therapy. Trametes versicolor is a traditional Chinese medicinal mushroom with a long history of being used to regulate immunity and prevent cancer. Its extractions were demonstrated with strong cell growth inhibitory activity on human colorectal tumor cells, while the anticancer activity of them is not acted through a direct cytotoxic effect. However, the intricacy and high molecular weight make mechanistic research difficult, which restricts their further application as a medication in clinical cancer treatment. Recent research has discovered a small molecule polysaccharide peptide derived from Trametes versicolor that has a distinct structure after decades of Trametes versicolor investigation. Uncertain molecular weight and a complex composition are problems that have been solved through studies on its structure, and it was demonstrated to have strong anti-proliferation activity on colorectal cancer in vitro and in vivo via interaction with EGFR signaling pathway. It opens up new horizons for research in this field, and these low molecular weight polysaccharide peptides provide a new insight of regulation of colorectal cancer proliferation and have great potential as drugs in the treatment of colorectal cancer. Full article

(This article belongs to the Special Issue Anticancer Activity and Metabolic Pathways of Natural Products)

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19 pages, 2716 KiB

Open AccessReview

Pharmacological Properties and Molecular Targets of Alisol Triterpenoids from Alismatis Rhizoma

by Christian Bailly

Biomedicines 2022, 10(8), 1945; https://doi.org/10.3390/biomedicines10081945 - 11 Aug 2022

Cited by 11 | Viewed by 2549

Abstract

More than 100 protostane triterpenoids have been isolated from the dried rhizomes of Alisma species, designated Alismatis rhizoma (AR), commonly used in Asian traditional medicine to treat inflammatory and vascular diseases. The main products are the alisols, with the lead compounds alisol-A/-B and [...] Read more.

More than 100 protostane triterpenoids have been isolated from the dried rhizomes of Alisma species, designated Alismatis rhizoma (AR), commonly used in Asian traditional medicine to treat inflammatory and vascular diseases. The main products are the alisols, with the lead compounds alisol-A/-B and their acetate derivatives being the most abundant products in the plant and the best-known bioactive products. The pharmacological effects of Ali-A, Ali-A 24-acetate, Ali-B, Ali-B 23-acetate, and derivatives have been analyzed to provide an overview of the medicinal properties, signaling pathways, and molecular targets at the origin of those activities. Diverse protein targets have been proposed for these natural products, including the farnesoid X receptor, soluble epoxide hydrolase, and other enzymes (AMPK, HCE-2) and functional proteins (YAP, LXR) at the origin of the anti-atherosclerosis, anti-inflammatory, antioxidant, anti-fibrotic, and anti-proliferative activities. Activities were classified in two groups. The lipid-lowering and anti-atherosclerosis effects benefit from robust in vitro and in vivo data (group 1). The anticancer effects of alisols have been largely reported, but, essentially, studies using tumor cell lines and solid in vivo data are lacking (group 2). The survey shed light on the pharmacological properties of alisol triterpenoids frequently found in traditional phytomedicines. Full article

(This article belongs to the Special Issue Anticancer Activity and Metabolic Pathways of Natural Products)

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16 pages, 2149 KiB

Open AccessEditor’s ChoiceReview

Naringin and Naringenin: Their Mechanisms of Action and the Potential Anticancer Activities

by Jolita Stabrauskiene, Dalia M. Kopustinskiene, Robertas Lazauskas and Jurga Bernatoniene

Biomedicines 2022, 10(7), 1686; https://doi.org/10.3390/biomedicines10071686 - 13 Jul 2022

Cited by 62 | Viewed by 8344

Abstract

Naringin and naringenin are the main bioactive polyphenols in citrus fruits, the consumption of which is beneficial for human health and has been practiced since ancient times. Numerous studies have reported these substances’ antioxidant and antiandrogenic properties, as well as their ability to [...] Read more.

Naringin and naringenin are the main bioactive polyphenols in citrus fruits, the consumption of which is beneficial for human health and has been practiced since ancient times. Numerous studies have reported these substances’ antioxidant and antiandrogenic properties, as well as their ability to protect from inflammation and cancer, in various in vitro and in vivo experimental models in animals and humans. Naringin and naringenin can suppress cancer development in various body parts, alleviating the conditions of cancer patients by acting as effective alternative supplementary remedies. Their anticancer activities are pleiotropic, and they can modulate different cellular signaling pathways, suppress cytokine and growth factor production and arrest the cell cycle. In this narrative review, we discuss the effects of naringin and naringenin on inflammation, apoptosis, proliferation, angiogenesis, metastasis and invasion processes and their potential to become innovative and safe anticancer drugs. Full article

(This article belongs to the Special Issue Anticancer Activity and Metabolic Pathways of Natural Products)

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