The apoptotic effect of nandrolone on human gastric (AGS) and colon (HCT) cancer cells and evaluation of iNOS, MMP9 expression level, and caspase-3, -8 and -9 activity

Abstract

Although androgens have been reported to induce apoptosis in cancer cells, there are few studies concerning with cytotoxic effects of nandrolone on human gastric (AGS) and colon (HCT) cancer cells. We evaluated the effects of nandrolone on apoptosis, iNOS, and MMP-9 expression level, and caspase-3, -8 and -9 activity in AGS and HCT cells. HCT and AGS cells were divided into control groups and groups treated with 0.625, 1.25, 2.5, 5 and 10 mg/ml of nandrolone. Cytotoxicity was measured using the MTT assay method. Flow cytometry was used to evaluate the apoptotic pathway that occurred in cells. The expression levels of iNOS and MMP-9 genes were evaluated using real-time PCR, and caspases activity was measured by the colourimetric method. Data were analyzed using ANOVA and an independent t-test. Cell viability significantly decreased in AGS and HCT cells treated with 2.5, 5 and 10 mg/ml of nandrolone. Treatment with the effective concentration of nandrolone (5.99 mg/ml) induced apoptosis in AGS and HCT cells and did not significantly alter the expression levels of iNOS and MMP-9 in AGS cells, however, led to a significant decrease in iNOS and MMP-9 expression levels in HCT cells. Activity levels of caspase-3, -8 and -9 significantly increased in AGS and HCT cells treated with the effective concentration of nandrolone. Higher concentrations of nandrolone had a significant cytotoxic effect and apoptotic pathway in AGS and HCT cells mediated by intrinsic and extrinsic pathways. It might also decrease the invasion and metastasis capability of colon cancer cells.