PurposeProgesterone 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 methodsIn 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.ResultsCompared 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.ConclusionsThe 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.

Background and Objectives: Researches have shown that progesterone influences the viability of breast cancer cells. The purpose of this study was to investigate the effect of progesterone on the viability of MCF-7 cell line and evaluation of Expression level of P53, Bax, and Bcl-2 Genes. Methods: In this laboratory-experimental study, MCF-7 cells were purchased from Pasture institute and divided into control group and the group received progesterone in the concentrations of 0.001, 0.01, 0.1, 1, and 10mg/mL. The viability of the cells was assessed using MTT assay. The relative expression level of P53, Bax, and Bcl-2 genes was investigated by Real Time PCR technique. Data analysis was performed using one-way ANOVA and independent samples t-test. Results: Exposure to 10mg/ml of progesterone resulted in decreased viability of MCF-7 cells compared to the control group (p<0.001). However, exposure to 0.001, 0.01, 0.1, and 1mg/ml of progesterone did not significantly alter the viability of the MCF-7 cells, as compared to the control group. The expression level of P53 and Bax genes significantly increased in MCF-7 cells exposed to the concentration 2.5mg/ml of progesterone compared to the control group (p<0.05 and p<0.001, respectively), but, the expression level of Bcl-2 gene significantly decreased compared to the control group (p<0.001). Conclusion: The results of this study revealed that high concentration of progesterone reduces the viability of MCF-7 cells and the cytotoxic effect of progesterone on MCF-7 cells is performed by induction of Bax dependent apoptosis and increased expression level of P53 tumor suppressor gene. Accordingly, progesterone is important in the treatment of breast cancer.