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Role of Phytochemicals and Structural Analogs in Cancer Chemoprevention and Therapeutics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 10016

Special Issue Editor

Prof. Dr. Hung Chi-Feng

E-Mail Website
Guest Editor
School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
Interests: cardiovascular; eye; natural products; pharmacology; skin

Special Issue Information

Dear Colleagues,

Cancer has always been the leading cause of death worldwide. Although there are many highly advanced treatments for cancer, chemotherapy still plays a vitally important role in this regard. The main ingredients of chemotherapy drugs are largely derived from plant ingredients, and these plant ingredients have exceptional therapeutic effects. Therefore, we hope that through the latest research, an increasing number of novel compound structures and mechanisms of action can be found. In the future, they will be used in some difficult-to-treat cancers. It is also hoped that, through more research, chemotherapeutic drugs with better pharmacokinetics can be developed.

Importantly, the exact active ingredient of a particular plant extract must be reported in the submitted research manuscripts, since papers describing the effects of mixed extractions from plants will not be accepted. Original research works, communications as well as reviews in the field are welcome for this Special Issue.

Prof. Dr. Hung Chi-Feng
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cardiovascular
  • eye
  • natural products
  • pharmacology
  • skin

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Published Papers (4 papers)

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Research

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18 pages, 5610 KiB  
Article
Anticancer and Targeting Activity of Phytopharmaceutical Structural Analogs of a Natural Peptide from Trichoderma longibrachiatum and Related Peptide-Decorated Gold Nanoparticles
by Francesca Moret, Luca Menilli, Celeste Milani, Giorgia Di Cintio, Chiara Dalla Torre, Vincenzo Amendola and Marta De Zotti
Int. J. Mol. Sci. 2023, 24(6), 5537; https://doi.org/10.3390/ijms24065537 - 14 Mar 2023
Cited by 4 | Viewed by 2030
Abstract
In the large field of bioactive peptides, peptaibols represent a unique class of compounds. They are membrane-active peptides, produced by fungi of the genus Trichoderma and known to elicit plant defenses. Among the short-length peptaibols, trichogin GA IV is nonhemolytic, proteolysis-resistant, antibacterial, and [...] Read more.
In the large field of bioactive peptides, peptaibols represent a unique class of compounds. They are membrane-active peptides, produced by fungi of the genus Trichoderma and known to elicit plant defenses. Among the short-length peptaibols, trichogin GA IV is nonhemolytic, proteolysis-resistant, antibacterial, and cytotoxic. Several trichogin analogs are endowed with potent activity against phytopathogens, thus representing a sustainable alternative to copper for plant protection. In this work, we tested the activity of trichogin analogs against a breast cancer cell line and a normal cell line of the same derivation. Lys-containing trichogins showed an IC50 below 12 µM, a peptide concentration not significantly affecting the viability of normal cells. Two analogs were found to be membrane-active but noncytotoxic. They were anchored to gold nanoparticles (GNPs) and further investigated for their ability to act as targeting agents. GNP uptake by cancer cells increased with peptide decoration, while it decreased in the corresponding normal epithelial cells. This work highlights the promising biological properties of peptaibol analogs in the field of cancer therapy either as cytotoxic molecules or as active targeting agents in drug delivery. Full article
(This article belongs to the Special Issue Role of Phytochemicals and Structural Analogs in Cancer Chemoprevention and Therapeutics)
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17 pages, 2139 KiB  
Article
Role of a Mixture of Polyphenol Compounds Released after Blueberry Fermentation in Chemoprevention of Mammary Carcinoma: In Vivo Involvement of miR-145
by Jean-François Mallet, Roghayeh Shahbazi, Nawal Alsadi, Ammar Saleem, Agnes Sobiesiak, John Thor Arnason and Chantal Matar
Int. J. Mol. Sci. 2023, 24(4), 3677; https://doi.org/10.3390/ijms24043677 - 12 Feb 2023
Cited by 10 | Viewed by 2832
Abstract
Epigenetic mechanisms such as microRNA (miRNA) deregulation seem to exert a central role in breast cancer initiation and progression. Therefore, targeting epigenetics deregulation may be an effective strategy for preventing and halting carcinogenesis. Studies have revealed the significant role of naturally occurring polyphenolic [...] Read more.
Epigenetic mechanisms such as microRNA (miRNA) deregulation seem to exert a central role in breast cancer initiation and progression. Therefore, targeting epigenetics deregulation may be an effective strategy for preventing and halting carcinogenesis. Studies have revealed the significant role of naturally occurring polyphenolic compounds derived from fermented blueberry fruits in cancer chemoprevention by modulation of cancer stem cell development through the epigenetic mechanism and regulation of cellular signaling pathways. In this study, we first investigated the phytochemical changes during the blueberry fermentation process. Fermentation favored the release of oligomers and bioactive compounds such as protocatechuic acid (PCA), gallic acid, and catechol. Next, we investigated the chemopreventive potentials of a polyphenolic mixture containing PCA, gallic acid, and catechin found in fermented blueberry juice in a breast cancer model by measuring miRNA expression and the signaling pathways involved in breast cancer stemness and invasion. To this end, 4T1 and MDA-MB-231 cell lines were treated with different doses of the polyphenolic mixture for 24 h. Additionally, female Balb/c mice were fed with this mixture for five weeks; two weeks before and three weeks after receiving 4T1 cells. Mammosphere formation was assayed in both cell lines and the single-cell suspension obtained from the tumor. Lung metastases were counted by isolating 6-thioguanine-resistant cells present in the lungs. In addition, we conducted RT-qPCR and Western blot analysis to validate the expression of targeted miRNAs and proteins, respectively. We found a significant reduction in mammosphere formation in both cell lines treated with the mixture and in tumoral primary cells isolated from mice treated with the polyphenolic compound. The number of colony-forming units of 4T1 cells in the lungs was significantly lower in the treatment group compared to the control group. miR-145 expression significantly increased in the tumor samples of mice treated with the polyphenolic mixture compared to the control group. Furthermore, a significant increase in FOXO1 levels was noted in both cell lines treated with the mixture. Overall, our results show that phenolic compounds found in fermented blueberry delay the formation of tumor-initiating cells in vitro and in vivo and reduce the spread of metastatic cells. The protective mechanisms seem to be related, at least partly, to the epigenetic modulation of mir-145 and its signaling pathways. Full article
(This article belongs to the Special Issue Role of Phytochemicals and Structural Analogs in Cancer Chemoprevention and Therapeutics)
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11 pages, 2069 KiB  
Article
Coriloxin Exerts Antitumor Effects in Human Lung Adenocarcinoma Cells
by Yu-Hsuan Kuo, Yi-Xuan Wang, Wan-Hua Peng, Nian-Yu Chi, Tzong-Huei Lee and Chi-Chung Wang
Int. J. Mol. Sci. 2022, 23(7), 3991; https://doi.org/10.3390/ijms23073991 - 3 Apr 2022
Cited by 1 | Viewed by 2129
Abstract
Both in Taiwan and around the world, lung cancer is a primary cause of cancer-related deaths. In Taiwan, the most prevalent form of lung cancer is lung adenocarcinoma, a type of non-small-cell lung carcinoma. Although numerous lung cancer therapies are available, their clinical [...] Read more.
Both in Taiwan and around the world, lung cancer is a primary cause of cancer-related deaths. In Taiwan, the most prevalent form of lung cancer is lung adenocarcinoma, a type of non-small-cell lung carcinoma. Although numerous lung cancer therapies are available, their clinical outcomes are unsatisfactory. Natural products, including fungal metabolites, are excellent sources of pharmaceutical compounds used in cancer treatment. We employed in vitro cell invasion, cell proliferation, cell migration, cell viability, and colony formation assays with the aim of evaluating the effects of coriloxin, isolated from fermented broths of Nectria balsamea YMJ94052402, on human lung adenocarcinoma CL1-5 and/or A549 cells. The potential targets regulated by coriloxin were examined through Western blot analysis. The cytotoxic effect of coriloxin was more efficiently exerted on lung adenocarcinoma cells than on bronchial epithelial cells. Moreover, low-concentration coriloxin significantly suppressed adenocarcinoma cells’ proliferative, migratory, and clonogenic abilities. These inhibitory effects were achieved through ERK/AKT inactivation, epithelial–mesenchymal transition regulation, and HLJ1 expression. Our findings suggest that coriloxin can be used as a multitarget anticancer agent. Further investigations of the application of coriloxin as an adjuvant therapy in lung cancer treatment are warranted. Full article
(This article belongs to the Special Issue Role of Phytochemicals and Structural Analogs in Cancer Chemoprevention and Therapeutics)
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Review

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27 pages, 7042 KiB  
Review
Enhanced Water Solubility and Anti-Tumor Activity of Oleanolic Acid through Chemical Structure Modification
by Zhicheng Gu, Shuxian Lin, Wanli Yan, Di Chen, Ziwei Zeng, Lei Chen, Yan Li and Bin He
Int. J. Mol. Sci. 2022, 23(21), 13291; https://doi.org/10.3390/ijms232113291 - 31 Oct 2022
Cited by 3 | Viewed by 2309
Abstract
Cancer has been a major health problem in the world in the past decades. It is urgent to develop new, effective and safe drugs for the treatment of cancer. There are many pentacyclic triterpenoids with positive anti-tumor activity and safety in nature. Oleanolic [...] Read more.
Cancer has been a major health problem in the world in the past decades. It is urgent to develop new, effective and safe drugs for the treatment of cancer. There are many pentacyclic triterpenoids with positive anti-tumor activity and safety in nature. Oleanolic acid (OA), as one of the pentacyclic triterpenoids, also has broad biological activities including liver protection, anti-inflammatory, hypoglycemic, antiviral and anti-tumor. Therefore, to investigate its anti-tumor activity and mechanism, many OA derivatives have been developed. Some derivatives are less toxic to normal hepatocytes, which may be due to the strong liver protection ability of OA. However, the poor water solubility of OA is one of the main reasons for the weak anti-tumor activity. It is reported that some OA derivatives could enhance solubility by chemically linking some hydrophilic groups to improve anti-tumor activity. This review not only summarizes the highly water-soluble OA derivatives that can improve anti-tumor activity reported in recent years, but also introduces their possible anti-tumor mechanisms. Full article
(This article belongs to the Special Issue Role of Phytochemicals and Structural Analogs in Cancer Chemoprevention and Therapeutics)
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