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Phytochemicals in Cancer Prevention and Therapy
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Phytochemicals in Cancer Prevention and Therapy

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 30524

Special Issue Editor

Prof. Dr. Min-Hsiung Pan

E-Mail Website
Guest Editor
Institute of Food Science & Technology, National Taiwan University, No.1, Sec.4, Roosevelt Road, Taipei 10617, Taiwan
Interests: cancer chemoprevention; anti-obesity; dietary natural bioactive compounds; anti-inflammation; carcinogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer and cancer-related diseases are multifactorial and the pursuit of cancer therapeutic targets and drug discovery is neverending. However, cancer drug use is always accompanied by side-effects and it is an aspiration to “make cancers preventable”. Phytochemicals are a befitting selection among suitable choices with lower costs, multiple sources, and, most importantly, less or no side-effects. Phytochemicals are powerful and some of them have reported effectiveness against various diseases in preclinical, clinical, and epidemiological research. In particular, the Special Issue focuses on the involvement of phytochemicals in the prevention and therapeutic action of cancer. As investigated previously, phytochemicals could be applied in cancer prevention and therapy via inflammatory response regulation, anti-carcinogenesis, anti-tumor, anti-metastasis, immunological modulation, gut microbiota modifications, etc. Herein, we are looking for the current research and great advances that may allow the potential of phytochemicals to be realized, understood, and carried forward in future studies. There is no limitation concerning the choice of cancer type or phytochemical, in terms of sources or classifications, as long as the criteria is met. Studies focusing on phytochemicals identification, modification, application, and strategies, including their safety, efficacy, and underlying molecular mechanisms and targets for cancer prevention and therapy are also welcome.

Prof. Dr. Min-Hsiung Pan
Guest Editor

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Keywords

  • Phytochemicals
  • Chemoprevention
  • Gut microbiota
  • Cancer therapy
  • Immunological modulation

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Published Papers (7 papers)

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Research

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18 pages, 3762 KiB  
Article
Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE/STAT3 Pathway
by Rong-Jane Chen, Yi-Jhen Lyu, Yu-Ying Chen, Yen-Chien Lee, Min-Hsiung Pan, Yuan-Soon Ho and Ying-Jan Wang
Molecules 2021, 26(21), 6741; https://doi.org/10.3390/molecules26216741 - 8 Nov 2021
Cited by 15 | Viewed by 3512
Abstract
The treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, because pro-survival signaling pathways—such as the receptor for advanced glycation end products (RAGE)/signal transducer and activator of transcription 3 (STAT3) pathway—are overexpressed in PDAC cells. Moreover, PDAC cells are highly resistant to [...] Read more.
The treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, because pro-survival signaling pathways—such as the receptor for advanced glycation end products (RAGE)/signal transducer and activator of transcription 3 (STAT3) pathway—are overexpressed in PDAC cells. Moreover, PDAC cells are highly resistant to chemotherapeutic agents because of autophagy induction. Therefore, autophagy and its modulated signaling pathways are attractive targets for developing novel therapeutic strategies for PDAC. Pterostilbene is a stilbenoid chemically related to resveratrol, and has potential for the treatment of cancers. Accordingly, we investigated whether the autophagy inhibitor chloroquine could potentiate the anticancer effect of pterostilbene in the PDAC cell lines MIA PaCa-2 and BxPC-3, as well as in an orthotopic animal model. The results indicated that pterostilbene combined with chloroquine significantly inhibited autophagy, decreased cell viability, and sensitized the cells to pterostilbene-induced apoptosis via downregulation of the RAGE/STAT3 and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways in PDAC cells. The results of the orthotopic animal model showed that pterostilbene combined with chloroquine significantly inhibited pancreatic cancer growth, delayed tumor quadrupling times, and inhibited autophagy and STAT3 in pancreatic tumors. In summary, the present study suggested the novel therapeutic strategy of pterostilbene combined with chloroquine against the growth of pancreatic ductal adenocarcinoma by inhibiting autophagy and downregulating the RAGE/STAT3 signaling pathways. Full article
(This article belongs to the Special Issue Phytochemicals in Cancer Prevention and Therapy)
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15 pages, 10888 KiB  
Article
Identification of Novel Antagonists Targeting Cannabinoid Receptor 2 Using a Multi-Step Virtual Screening Strategy
by Mukuo Wang, Shujing Hou, Ye Liu, Dongmei Li and Jianping Lin
Molecules 2021, 26(21), 6679; https://doi.org/10.3390/molecules26216679 - 4 Nov 2021
Cited by 4 | Viewed by 2580
Abstract
The endocannabinoid system plays an essential role in the regulation of analgesia and human immunity, and Cannabinoid Receptor 2 (CB2) has been proved to be an ideal target for the treatment of liver diseases and some cancers. In this study, we identified CB2 [...] Read more.
The endocannabinoid system plays an essential role in the regulation of analgesia and human immunity, and Cannabinoid Receptor 2 (CB2) has been proved to be an ideal target for the treatment of liver diseases and some cancers. In this study, we identified CB2 antagonists using a three-step “deep learning–pharmacophore–molecular docking” virtual screening approach. From the ChemDiv database (1,178,506 compounds), 15 hits were selected and tested by radioligand binding assays and cAMP functional assays. A total of 7 out of the 15 hits were found to exhibit binding affinities in the radioligand binding assays against CB2 receptor, with a pKi of 5.15-6.66, among which five compounds showed antagonistic activities with pIC50 of 5.25–6.93 in the cAMP functional assays. Among these hits, Compound 8 with the 4H-pyrido[1,2-a]pyrimidin-4-one scaffold showed the best binding affinity and antagonistic activity with a pKi of 6.66 and pIC50 of 6.93, respectively. The new scaffold could serve as a lead for further development of CB2 drugs. Additionally, we hope that the model in this study could be further utilized to identify more novel CB2 receptor antagonists, and the developed approach could also be used to design potent ligands for other therapeutic targets. Full article
(This article belongs to the Special Issue Phytochemicals in Cancer Prevention and Therapy)
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29 pages, 35816 KiB  
Article
Type-3 Hyaluronan Synthase Attenuates Tumor Cells Invasion in Human Mammary Parenchymal Tissues
by Wen-Jui Lee, Shih-Hsin Tu, Tzu-Chun Cheng, Juo-Han Lin, Ming-Thau Sheu, Ching-Chuan Kuo, Chun A. Changou, Chih-Hsiung Wu, Hui-Wen Chang, Hang-Lung Chang, Li-Ching Chen and Yuan-Soon Ho
Molecules 2021, 26(21), 6548; https://doi.org/10.3390/molecules26216548 - 29 Oct 2021
Cited by 1 | Viewed by 2275
Abstract
The microenvironment for tumor growth and developing metastasis should be essential. This study demonstrated that the hyaluronic acid synthase 3 (HAS3) protein and its enzymatic product hyaluronic acid (HA) encompassed in the subcutaneous extracellular matrix can attenuate the invasion of human breast tumor [...] Read more.
The microenvironment for tumor growth and developing metastasis should be essential. This study demonstrated that the hyaluronic acid synthase 3 (HAS3) protein and its enzymatic product hyaluronic acid (HA) encompassed in the subcutaneous extracellular matrix can attenuate the invasion of human breast tumor cells. Decreased HA levels in subcutaneous Has3-KO mouse tissues promoted orthotopic breast cancer (E0771) cell-derived allograft tumor growth. MDA-MB-231 cells premixed with higher concentration HA attenuate tumor growth in xenografted nude mice. Human patient-derived xenotransplantation (PDX) experiments found that HA selected the highly migratory breast cancer cells with CD44 expression accumulated in the tumor/stroma junction. In conclusion, HAS3 and HA were detected in the stroma breast tissues at a high level attenuates effects for induced breast cancer cell death, and inhibit the cancer cells invasion at the initial stage. However, the highly migratory cancer cells were resistant to the HA-mediated effects with unknown mechanisms. Full article
(This article belongs to the Special Issue Phytochemicals in Cancer Prevention and Therapy)
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16 pages, 2731 KiB  
Article
A Natural Degradant of Curcumin, Feruloylacetone Inhibits Cell Proliferation via Inducing Cell Cycle Arrest and a Mitochondrial Apoptotic Pathway in HCT116 Colon Cancer Cells
by Yu-Ting Chou, Yen-Chun Koh, Kalyanam Nagabhushanam, Chi-Tang Ho and Min-Hsiung Pan
Molecules 2021, 26(16), 4884; https://doi.org/10.3390/molecules26164884 - 12 Aug 2021
Cited by 12 | Viewed by 2857
Abstract
Feruloylacetone (FER) is a natural degradant of curcumin after heating, which structurally reserves some functional groups of curcumin. It is not as widely discussed as its original counterpart has been previously; and in this study, its anticancer efficacy is investigated. This study focuses [...] Read more.
Feruloylacetone (FER) is a natural degradant of curcumin after heating, which structurally reserves some functional groups of curcumin. It is not as widely discussed as its original counterpart has been previously; and in this study, its anticancer efficacy is investigated. This study focuses on the suppressive effect of FER on colon cancer, as the efficacious effect of curcumin on this typical cancer type has been well evidenced. In addition, demethoxy-feruloylacetone (DFER) was applied to compare the effect that might be brought on by the structural differences of the methoxy group. It was revealed that both FER and DFER inhibited the proliferation of HCT116 cells, possibly via suppression of the phosphorylated mTOR/STAT3 pathway. Notably, FER could significantly repress both the STAT3 phosphorylation and protein levels. Furthermore, both samples showed capability of arresting HCT116 cells at the G2/M phase via the activation of p53/p21 and the upregulation of cyclin-B. In addition, ROS elevation and changes in mitochondrial membrane potential were revealed, as indicated by p-atm elevation. The apoptotic rate rose to 36.9 and 32.2% after being treated by FER and DFER, respectively. In summary, both compounds exhibited an anticancer effect, and FER showed a greater proapoptotic effect, possibly due to the presence of the methoxy group on the aromatic ring. Full article
(This article belongs to the Special Issue Phytochemicals in Cancer Prevention and Therapy)
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Review

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27 pages, 4337 KiB  
Review
Phytochemicals from Polyalthia Species: Potential and Implication on Anti-Oxidant, Anti-Inflammatory, Anti-Cancer, and Chemoprevention Activities
by Yung-Chia Chen, Yi-Chen Chia and Bu-Miin Huang
Molecules 2021, 26(17), 5369; https://doi.org/10.3390/molecules26175369 - 3 Sep 2021
Cited by 14 | Viewed by 4334
Abstract
Polyalthia belong to the Annonaceae family and are a type of evergreen tree distributed across many tropical and subtropical regions. Polyalthia species have been used long term as indigenous medicine to treat certain diseases, including fever, diabetes, infection, digestive disease, etc. Recent studies [...] Read more.
Polyalthia belong to the Annonaceae family and are a type of evergreen tree distributed across many tropical and subtropical regions. Polyalthia species have been used long term as indigenous medicine to treat certain diseases, including fever, diabetes, infection, digestive disease, etc. Recent studies have demonstrated that not only crude extracts but also the isolated pure compounds exhibit various pharmacological activities, such as anti-oxidant, anti-microbial, anti-tumor, anti-cancer, etc. It is known that the initiation of cancer usually takes several years and is related to unhealthy lifestyle, as well as dietary and environmental factors, such as stress, toxins and smoking. In fact, natural or synthetic substances have been used as cancer chemoprevention to delay, impede, or even stop cancer growing. This review is an attempt to collect current available phytochemicals from Polyalthia species, which exhibit anti-cancer potentials for chemoprevention purposes, providing directions for further research on the interesting agents and possible clinical applications. Full article
(This article belongs to the Special Issue Phytochemicals in Cancer Prevention and Therapy)
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20 pages, 2632 KiB  
Review
The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin
by Yu-Ying Chen, Chun-Hsien Chen, Wei-Chen Lin, Chih-Wei Tung, Yung-Chia Chen, Shang-Hsun Yang, Bu-Miin Huang and Rong-Jane Chen
Molecules 2021, 26(16), 4954; https://doi.org/10.3390/molecules26164954 - 16 Aug 2021
Cited by 18 | Viewed by 5830
Abstract
Cordycepin is an adenosine derivative isolated from Cordyceps sinensis, which has been used as an herbal complementary and alternative medicine with various biological activities. The general anti-cancer mechanisms of cordycepin are regulated by the adenosine A3 receptor, epidermal growth factor receptor (EGFR), [...] Read more.
Cordycepin is an adenosine derivative isolated from Cordyceps sinensis, which has been used as an herbal complementary and alternative medicine with various biological activities. The general anti-cancer mechanisms of cordycepin are regulated by the adenosine A3 receptor, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), and glycogen synthase kinase (GSK)-3β, leading to cell cycle arrest or apoptosis. Notably, cordycepin also induces autophagy to trigger cell death, inhibits tumor metastasis, and modulates the immune system. Since the dysregulation of autophagy is associated with cancers and neuron, immune, and kidney diseases, cordycepin is considered an alternative treatment because of the involvement of cordycepin in autophagic signaling. However, the profound mechanism of autophagy induction by cordycepin has never been reviewed in detail. Therefore, in this article, we reviewed the anti-cancer and health-promoting effects of cordycepin in the neurons, kidneys, and the immune system through diverse mechanisms, including autophagy induction. We also suggest that formulation changes for cordycepin could enhance its bioactivity and bioavailability and lower its toxicity for future applications. A comprehensive understanding of the autophagy mechanism would provide novel mechanistic insight into the anti-cancer and health-promoting effects of cordycepin. Full article
(This article belongs to the Special Issue Phytochemicals in Cancer Prevention and Therapy)
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Graphical abstract

29 pages, 1164 KiB  
Review
New Insights into Molecular Mechanism behind Anti-Cancer Activities of Lycopene
by Boon-Peng Puah, Juriyati Jalil, Ali Attiq and Yusof Kamisah
Molecules 2021, 26(13), 3888; https://doi.org/10.3390/molecules26133888 - 25 Jun 2021
Cited by 65 | Viewed by 7938
Abstract
Lycopene is a well-known compound found commonly in tomatoes which brings wide range of health benefits against cardiovascular diseases and cancers. From an anti-cancer perspective, lycopene is often associated with reduced risk of prostate cancer and people often look for it as a [...] Read more.
Lycopene is a well-known compound found commonly in tomatoes which brings wide range of health benefits against cardiovascular diseases and cancers. From an anti-cancer perspective, lycopene is often associated with reduced risk of prostate cancer and people often look for it as a dietary supplement which may help to prevent cancer. Previous scientific evidence exhibited that the anti-cancer activity of lycopene relies on its ability to suppress oncogene expressions and induce proapoptotic pathways. To further explore the real potential of lycopene in cancer prevention, this review discusses the new insights and perspectives on the anti-cancer activities of lycopene which could help to drive new direction for research. The relationship between inflammation and cancer is being highlighted, whereby lycopene suppresses cancer via resolution of inflammation are also discussed herein. The immune system was found to be a part of the anti-cancer system of lycopene as it modulates immune cells to suppress tumor growth and progression. Lycopene, which is under the family of carotenoids, was found to play special role in suppressing lung cancer. Full article
(This article belongs to the Special Issue Phytochemicals in Cancer Prevention and Therapy)
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