Mechanisms by Which Equol Enhances The Proliferation of Cisplatin-Resistant Gastric Cancer Cells

Gastric carcinoma, originating from the epithelium of the gastric mucosa, is a malignant tumor. Cisplatin, a commonly used platinum-based metal complex, plays a signifinant role in its anticancer activity due to the platinum atom in its molecular structure. It is a first-line treatment drug with broad application prospects for various solid tumors, including gastric carcinoma. However, the development of drug resistance and unavoidable toxic side effects associated with increasing treatment doses have to some extent affected the clinical efficacy of cisplatin. Therefore, it is of great researchsignificance to search for low-toxicity and broad-targeted anti-gastric carcinoma drugs from natural products to improve the sensitivity of gastric carcinoma cells to cisplatin.

Cisplatin is currently a commonly used platinum-based complex in cancer treatment, and the platinum atom in the molecule plays a significant role in its anti-tumor effect. However, only the cis isomer is effective, while the trans isomer is ineffective.Cisplatin can form cross-links with DNA strands, exhibiting cytotoxic effects on cells. It can penetrate through the charged cell membrane in the body without the need for carrier transport. Cisplatin has advantages such as a broad spectrum of anticanceractivity, effectiveness against hypoxic cells, and strong therapeutic effects.When used in combination with etoposide, cyclophosphamide, and 5-fluorouracil, cisplatin has shown significant efficacy in the treatment of malignant lymphoma, breast cancer, head and neck squamous cell carcinoma, thyroid cancer, and osteosarcoma.

In order to study the effects of the combination of equol and cisplatin on the proliferation and apoptosis of human gastric cancer cells and its mechanism of action in vitro, the researchers applied different concentrations of equol and cisplatin alone or in combination to human gastric cancer MGC-803 cells, and then detected the cell viability, apoptosis, and P-gp protein by different assays, and the results were asfollows:

1.Equol enhances the antiproliferative activity of cisplatin

2.Equol enhances the apoptotic effect of cisplatin

3.Equol inhibited cisplatin-induced P-gp protein expression in a time- and dose-dependent manner.

In summary, the combination of equol and cisplatin showed stronger antiproliferative and pro-apoptotic effects than cisplatin alone, and the combination of the two has synergistic anti-tumor effects; equol can also inhibit the increase of P-gp protein caused by cisplatin.This study provides a new therapeutic idea to improve the sensitivity of gastric cancer cells to cisplatin, and needs further research.

References:

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[2]  D. E L . Determination of S- and/or R-equol in plant-based food products and efficacy of topical or oral 4′,7-isoflavandiol (R/S equol) to improve skin health in adult men, a Placebo-controlled pilot study [J].  Journal of Functional Foods, 2021, 83 .