Cytotoxic and Apoptotic Effects of Govaniadine Isolated from Wall. Roots on Human Breast Cancer (MCF-7) Cells.

Current breast cancer therapies have limitations in terms of increased drug resistance resulting in short-term efficacy, thus demanding the discovery of new therapeutic agents. In this study, cytotoxic activity and apoptotic effects of govaniadine isolated from Wall. roots were determined on human breast cancer (MCF-7) cells. The SRB assay result revealed that govaniadine led to dose- and time-dependent cytotoxic effect in MCF-7 cells along with less cytotoxicity against MCF-10A cells. Govaniadine-induced apoptosis was also accompanied by upregulation of , , and mRNA expression as assessed by real time PCR analysis. Flow cytometric analysis with Annexin V and PI staining indicated that govaniadine is a potent inducer of apoptosis in MCF-7 cell lines. Distinctive morphological changes contributed to apoptosis and DNA laddering were observed in govaniadine-treated MCF-7 cells. Caspase-7 was significantly activated in treated MCF-7 cells. Govaniadine-treated MCF-7 cells also showed enhanced levels of intracellular reactive oxygen species (ROS) and glutathione S-transferase (GST) and decreased levels of glutathione (GSH). The results indicate that govaniadine has potent and selective cytotoxic effects against MCF-7 cells and the potential to induce caspase 7 dependent apoptosis in MCF-7 cells by activation of pathways that lead to oxidative stress.