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

Abstract

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 Ca²⁺ 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 G₁ 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 Ca²⁺ homeostasis, that was restored by diphenyleneiodonium, a mitochondrial ROS inhibitor and verapamil, a Ca²⁺ 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 Ca²⁺-dependent apoptosis, respectively.

Keywords: Ca2+ homeostasis; ROS production; apoptosis; monensin.