Monensin Induces PC-3 Prostate Cancer Cell Apoptosis via ROS Production and Ca2+ Homeostasis Disruption.

BACKGROUND

Monensin is a carboxyl polyether ionophore that potently inhibits the growth of various cancer cells. Recently, the anticancer effects of monensin have been recognized based on its ability to induce apoptosis in cancer cells. However, anticancer effect of monensin and its mechanism of action have yet to be investigated, especially against human prostate cancer cells.

MATERIALS AND METHODS

Cell viability assay, western blot, cell-cycle arrest, annexin V/propidium iodide assay, reactive oxygen species (ROS) production and intracellular Ca flux were assayed.

RESULTS

In this study, monensin significantly inhibited cell viability in a dose-dependent manner in prostate cell lines. Moreover, cell growth inhibition by monensin induced G phase cell-cycle arrest and apoptosis via regulation of cell cycle- and apoptosis-related proteins in PC-3 cells. In addition, monensin induced the production of ROS and the disruption of Ca homeostasis, that was restored by diphenyleneiodonium, a mitochondrial ROS inhibitor and verapamil, a Ca channel blocker, respectively, as confirmed by pro-caspase-3 activation and poly ADP ribose polymerase cleavage.

CONCLUSION

Monensin induces cell-cycle arrest and apoptosis through regulation of cell cycle- and apoptosis-related proteins, resulting in induction of mitochondrial ROS- and Ca-dependent apoptosis, respectively.