Myricanol-9-acetate, a Novel Naturally Occurring Derivative of Myricanol, Induces ROS-dependent Mitochondrial-mediated Apoptosis in MCF-7 Cancer Cells

Title:Myricanol-9-acetate, a Novel Naturally Occurring Derivative of Myricanol, Induces ROS-dependent Mitochondrial-mediated Apoptosis in MCF-7 Cancer Cells

Volume: 21 Issue: 15

Author(s): Gazanfar Ahmad, Sameer Ahmad Mir, Loveleena K. Anand, Faheem H. Pottoo, Neerupma Dhiman*, Fayaz Malik*Asif Ali*

Affiliation:

• Amity Institute of Pharmacy, Amity University, Noida, UP 201301,India

• Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, J&K190005,India

• Natural Product Laboratory, CSIR-IIIM, Jammu, J&K 180001,India

Keywords: Cancer, Myrica esculenta, Myricaol-9-acetate, Bcl2, G0/G1 phase cell cycle phase, Apoptosis.

Abstract:

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.

Cite this article as:

Ahmad Gazanfar, Mir Ahmad Sameer, Anand K. Loveleena, Pottoo H. Faheem, Dhiman Neerupma*, Malik Fayaz*, Ali Asif*, Myricanol-9-acetate, a Novel Naturally Occurring Derivative of Myricanol, Induces ROS-dependent Mitochondrial-mediated Apoptosis in MCF-7 Cancer Cells, Current Topics in Medicinal Chemistry 2021; 21 (15) . https://dx.doi.org/10.2174/1568026621666210615151358