Inhibition of Gastric Cancer Cell Growth and Proliferation by Genistein

Background and Objective: Compelling evidence exists in favor of the effectiveness of herbal plant-derived components in cancer treatment; however their exact mechanisms of action are not well understood. Since the alteration of mitogen-activated protein kinase enzymes (MAPKs) has been reported in different cancer types, the present study aimed to investigate the effects of soy isoflavonoid genistein on the inhibition of cell viability and proliferation of AGS gastric cancer cell line by determining p۳۸MAPK gene expression and also protein levels. Materials and Methods: Cell viability was determined by MTT assay at different genistein concentrations (۰, ۵۰, ۷۰, and ۹۰ µM) after ۲۴ hours of incubation. Quantitative Real-time PCR was carried out to obtain p۳۸MAPK gene expression levels and its active phosphorylated protein (p-p۳۸MAPK) was measured by flow cytometry. Results: Genistein significantly reduced cell viability in a concentration and time-dependent manner.  Exposure of gastric cancer cells to ۰, ۵۰, ۷۰, and ۹۰ µM genistein down-regulated p۳۸MAPK gene expression by ۸۳, ۵۶, and ۵۷%, and reduced cell proliferation by ۳۵, ۵۲, and ۶۷%, respectively.  In addition, a great reduction was observed in p-p۳۸MAPK protein levels in treated cells compared to untreated control cells. Conclusion: Since different concentrations of genistein reduced p۳۸MAPK gene expression and lowered proliferation of AGS gastric cancer cells, it might be a potent candidate for a therapeutic plant-derived agent for combination therapy in gastric cancer.

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Keywords: Apoptosis , Gastric neoplasms , Gene expression , Genistein , p۳۸ mitogen-activated protein kinase , Proliferation