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, Delta Psi m loss, ROS generation, western blot assay, 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 IC(50)20 mu M with MA treatment as compared to the IC50 of 42 mu M for myricanol treatment. Detailed mechanistic studies revealed that MA induces apoptosis of MCF-7 cell line through ROS generation and dose-dependent drop in mitochondrial membrane potential associated with cell cycle arrest at G0/G1 phase. Our results further demonstrated that down-regulation of Bcl2 and activation of the caspase cascade are 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 mu M of MA, thus, supporting our results.Conclusion: Present findings suggest that MA might serve as a promising novel drug candidate with high scope for taking it to further evaluation in preclinical and clinical studies.