Progesterone inhibits growth and induces apoptosis in cancer cells through modulation of reactive oxygen species.

OBJECTIVE

Progesterone (P4) has been implicated as a protective factor for ovarian and endometrial cancers, yet little is known about its mechanism of action. We have shown apoptosis in ovarian and endometrial cancer cells with high doses of P4. Increased generation of reactive oxygen species (ROS) and an altered redox status have long been observed in cancer cells. The goal of this study was to assess the effect of P4 on cell growth, ROS generation, oxidative stress markers, and the expression of antioxidant proteins.

METHODS

All experiments were performed in vitro using cancer cell lines. Cell proliferation was determined using MTS proliferation assay. Production of ROS in cells was measured with the ROS indicator dye, aminophenyl fluorescein. Alterations in expression of antioxidant and apoptotic proteins were assessed by Western blotting.

RESULTS

The exposure of ovarian and endometrial cancer cell cultures to various doses of P4 caused a dose-dependent decrease in cell viability and the activation of caspase-3. Levels of ROS, markers of oxidative stress, and antioxidant proteins were elevated in cancer cells compared to normal cells and a marked decrease in their expression was seen following P4 treatment. In cancer cells, ROS was elevated while p-53 expression was low. P4 exposure of cells resulted in increased p-53 and BAX and decreased BCL-2 expression.

CONCLUSIONS

The data indicates that P4 has antioxidant effects. It alleviates ROS stress and causes apoptosis by upregulating proapoptotic (p-53 and BAX) and decreasing antiapoptotic (BCL-2) gene expression in cancer cells. These findings could have potential therapeutic implications.