Involvement of Caspase-3 Pathway in Anti-cancer Properties of Genistein in AGS Gastric Cancer Cell Line is Still Enigmatic

Abstract

Background: Genistein is an isoflavone that has been reported to have various anti-cancer properties. Objectives: This study aimed to reveal whether or not the anti-cancer properties of genistein in AGS gastric cancer cell line were mediated through caspase-3 enzyme. Methods: AGS gastric cancer cells were treated with different concentrations of genistein for 12, 24, and 48 hours and, then, the viability of the cells and IC50 were determined. To determine the effect of genistein on AGS cell migration potency, the wound healing assay was performed. The genistein-induced apoptosis in AGS gastric cells was evaluated by flow cytometry. Caspase-3 gene (CASP3) expression level and its enzyme activity level were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and colorimetric techniques, respectively. Results: The IC50 value was calculated as 70 μM concentration for 24 hours of incubation with genistein. Genistein significantly reduced AGS cell migration compared to the untreated control cells (P < 0.001). Genistein increased the early and late apoptosis of the cells (P < 0.001) and upregulated the caspase-3 gene expression (P < 0.001), but did not significantly enhance the caspase-3 enzyme activity in treated cells. Conclusion: Genistein exhibited anti-cancer effects on AGS cells to some extent by reducing cellular migration, increasing apoptosis, and upregulating CASP3 gene expression; however, it did not alter the caspse-3 activity. Therefore, it was recommended that more studies should be carried out to delineate the role of caspase-3 in health benefits attributed to the genistein.

Keywords

• apoptosis
• caspase 3
• cell proliferation
• gastric neoplasms
• genistein