The apoptotic effects of progesterone on breast cancer (MCF-7) and human osteosarcoma (MG-636) cells.

PURPOSE

Progesterone has been reported to inhibit the proliferation of breast cancer and osteosarcoma cells; however, its inhibitory mechanism has not yet been clarified. The aim of the present study was to clarify the effects of progesterone on apoptosis in breast cancer (MCF-7) and human osteosarcoma (MG-63) cells.

MATERIALS AND METHODS

In this experimental study the cytotoxic effect of progesterone was measured in MCF-7 and MG-63 cells exposed to different concentrations of progesterone using MTT assay, and effective concentrations were identified. The expression levels of the Bax, P53 and Bcl-2 genes were evaluated by real-time PCR, and caspase-3, 8 and 9 activity levels were determined using a colorimetric method. Hoechst staining and flow cytometry were used to confirm apoptosis. The data were statistically analyzed using one-way analysis of variance (ANOVA) and independent-samples t-test.

RESULTS

Compared to the control group, we observed a significant increase in the expression levels of the Bax and P53 genes and the activity levels of caspase-3 and 9, and a significant decrease in the expression level of the Bcl-2 gene in MCF-7 and MG-63 treated with effective concentration of progesterone. The caspase-8 activity level did not change significantly in treated MG-63 but increased in treated MCF-7 cells. Hoechst staining and flow cytometry results confirmed apoptosis in the cells exposed to effective concentration of progesterone.

CONCLUSIONS

The cytotoxic effect of progesterone on breast cancer and osteosarcoma cells was mediated by apoptotic pathways. In this context, progesterone triggers the extrinsic and intrinsic apoptotic pathways in MCF-7 cells and induces the intrinsic apoptotic pathway in MG-63 cells.