Benzoxazinoids in human diet: an anti-cancer agent?

Background: Targeting evolutionarily conserved proteins in malignant cells and the adapter proteins involved in signalling that generates from such proteins may play a cardinal role in the selection of anti-cancer drugs. Drugs targeting these proteins could be of importance in developing anti-cancer drugs. Objectives: We inferred that drugs like loperamide and promethazine that act as antagonists of proteins conserved in cancer cells like voltage-gated Calcium channels (Cav), Calmodulin (CaM) and drug efflux (ABCB1) pump may have the potential to be re-purposed as an anti-cancer agent in Prostate Cancer (PCa). Methods: Growth and cytotoxic assays were performed by selecting loperamide and promethazine to target Cav, CaM and drug efflux (ABCB1) pumps to elucidate their effects on androgen-independent PC3 and DU145 PCa cell lines. Results: We show that loperamide and promethazine in doses of 80-100μg/ml exert oncocidal effects when tested in DU145 and PC3 cell lines. Diphenhydramine, which shares its targets with promethazine, except the CaM, failed to exhibit oncocidal effects. Conclusion: Anti-cancer effects can be of significance if structural analogues of loperamide and promethazine that specifically target Cav, CaM and ABCB1 drug efflux pumps can be synthesized, or these two drugs could be re-purposed after human trials in PCa.

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Calotropis procera (Aiton) Dryand (Apocynaceae) as an anti-cancer agent against canine mammary tumor and osteosarcoma cells

Research in Veterinary Science ◽

10.1016/j.rvsc.2021.06.005 ◽

2021 ◽

Author(s):

Ana CarolinaSilveira Rabelo ◽

Jéssica Borghesi ◽

Ana Claudia O. Carreira ◽

Rafael Gonçalves Hayashi ◽

Fernanda Bessa ◽

...

Keyword(s):

Mammary Tumor ◽

Calotropis Procera ◽

Canine Mammary Tumor ◽

Osteosarcoma Cells ◽

Anti Cancer ◽

Cancer Agent

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Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02012-7 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Jingjing Yang ◽

Yulu Zhou ◽

Shuduo Xie ◽

Ji Wang ◽

Zhaoqing Li ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Treatment ◽

Morphological Changes ◽

Tumor Model ◽

Independent Manner ◽

Regulated Cell Death ◽

Anti Cancer ◽

Cancer Agent ◽

Approved Drugs

Abstract Background Ferroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation of lipid peroxidation and is involved in various pathophysiological conditions, including cancer. Targeting ferroptosis is considered to be a novel anti-cancer strategy. The identification of FDA-approved drugs as ferroptosis inducers is proposed to be a new promising approach for cancer treatment. Despite a growing body of evidence indicating the potential efficacy of the anti-diabetic metformin as an anti-cancer agent, the exact mechanism underlying this efficacy has not yet been fully elucidated. Methods The UFMylation of SLC7A11 is detected by immunoprecipitation and the expression of UFM1 and SLC7A11 in tumor tissues was detected by immunohistochemical staining. The level of ferroptosis is determined by the level of free iron, total/lipid Ros and GSH in the cells and the morphological changes of mitochondria are observed by transmission electron microscope. The mechanism in vivo was verified by in situ implantation tumor model in nude mice. Results Metformin induces ferroptosis in an AMPK-independent manner to suppress tumor growth. Mechanistically, we demonstrate that metformin increases the intracellular Fe2+ and lipid ROS levels. Specifically, metformin reduces the protein stability of SLC7A11, which is a critical ferroptosis regulator, by inhibiting its UFMylation process. Furthermore, metformin combined with sulfasalazine, the system xc− inhibitor, can work in a synergistic manner to induce ferroptosis and inhibit the proliferation of breast cancer cells. Conclusions This study is the first to demonstrate that the ability of metformin to induce ferroptosis may be a novel mechanism underlying its anti-cancer effect. In addition, we identified SLC7A11 as a new UFMylation substrate and found that targeting the UFM1/SLC7A11 pathway could be a promising cancer treatment strategy.

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Mangiferin as New Potential Anti-Cancer Agent and Mangiferin-Integrated Polymer Systems—A Novel Research Direction

Biomolecules ◽

10.3390/biom11010079 ◽

2021 ◽

Vol 11 (1) ◽

pp. 79

Author(s):

Svetlana N. Morozkina ◽

Thi Hong Nhung Vu ◽

Yuliya E. Generalova ◽

Petr P. Snetkov ◽

Mayya V. Uspenskaya

Keyword(s):

Molecular Mechanisms ◽

Biological Activities ◽

Research Direction ◽

Biological Action ◽

The Body ◽

Biologically Active ◽

Polymer Systems ◽

Anti Cancer ◽

Long Time ◽

Cancer Agent

For a long time, the pharmaceutical industry focused on natural biologically active molecules due to their unique properties, availability and significantly less side-effects. Mangiferin is a naturally occurring C-glucosylxantone that has substantial potential for the treatment of various diseases thanks to its numerous biological activities. Many research studies have proven that mangiferin possesses antioxidant, anti-infection, anti-cancer, anti-diabetic, cardiovascular, neuroprotective properties and it also increases immunity. It is especially important that it has no toxicity. However, mangiferin is not being currently applied to clinical use because its oral bioavailability as well as its absorption in the body are too low. To improve the solubility, enhance the biological action and bioavailability, mangiferin integrated polymer systems have been developed. In this paper, we review molecular mechanisms of anti-cancer action as well as a number of designed polymer-mangiferin systems. Taking together, mangiferin is a very promising anti-cancer molecule with excellent properties and the absence of toxicity.

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