Myricanol-9-acetate, a novel naturally occurring derivative of myricanol, induces ROS-dependent mitochondrial-mediated Apoptosis in MCF-7 cancer cells.

Background Low therapeutic efficacy and drug-induced systemic toxicity of currently used anti-cancerous chemotherapeutic agents are major compelling factors for finding out clinically efficient molecules with high efficiency and less toxicity. Objective The current research work was undertaken to evaluate the anticancer potential of Myricanol-9-acetate (MA), a novel naturally occurring derivative of myricanol. Methods MCF-7, MiaPaCa-2, and HCT 116 were used for cytotoxicity determination of the MA and ML (Myricanol) by MTT assay. The mechanistic study involved the determination of cell cycle arrest, ΔΨm loss, ROS generation, western blot assay, and flow cytometry by reported methods on MCF-7 cells. Results MA exhibited anticancer activity against all three cell lines; however, the molecule was found most active against the MCF-7 cell line. We observed IC50 20μM with MA treatment as compared to the IC50 of 42 μM for myricanol treatment. Detailed mechanistic studies revealed that MA induced apoptosis on MCF-7 cell line through ROS generation; a dose-dependent drop in mitochondrial membrane potential was found to be associated with cell cycle arrest at G0/G1 phase. Our results further demonstrated down-regulation of Bcl2 and activation of the caspase cascade as the events involved in the MA-induced apoptosis. Flow cytometry results indicated an increase in early and late apoptotic population in a dose-dependent manner with an apoptotic population of about 20% at 30 μM of MA, thus supporting our results. Conclusion Present findings thus suggest that MA might serve as a promising novel drug candidate having high scope for further evaluation in preclinical and clinical studies.