Myricanol-9-acetate, a Novel Naturally Occurring Derivative of Myricanol, Induces ROS-dependent
Gazanfar Ahmad1, Sameer Ahmad Mir2, Loveleena K Anand2
1Amity Institute of Pharmacy, Amity University, Noida, UP 201301, India.
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, 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 IC5020 μM with MA treatment as compared to the IC50 of 42 μM 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 μM 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.
