Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

Title:Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

Volume: 18 Issue: 9

Author(s): Manjula Devi Ramamoorthy, Ashok Kumar, Mahesh Ayyavu and Kannan Narayanan Dhiraviam*

Affiliation:

• Department of Plant Biotechnology, School of Biotechnology, Madurai Kamaraj University, Madurai-625021, Tamilnadu,India

Keywords: Rauwolfia serpentina, caspase, cell cycle, reactive oxygen species, molecular docking, mitochondrial membrane.

Abstract: Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive.

Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis.

Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results.

Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

Cite this article as:

Ramamoorthy Devi Manjula , Kumar Ashok, Ayyavu Mahesh and Dhiraviam Narayanan Kannan *, Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (9) . https://dx.doi.org/10.2174/1871520618666180209152215