Nisin induces apoptosis in cervical cancer cells via reactive oxygen species generation and mitochondrial membrane potential changes

Nisin, an antimicrobial peptide produced by Lactococcus lactis, is widely used as a safe food preservative and has been recently attracting the attention of many researchers as a potential anticancer agent. The cytotoxicity of nisin against HeLa, OVCAR-3, SK-OV-3, and HUVEC cells was evaluated using MTT assay. The apoptotic effect of nisin was identified by Annexin-V/propidium iodide assay, and then it was further confirmed by western blotting analysis, mitochondrial membrane potential (ΔΨm) analysis, and reactive oxygen species (ROS) assay. The MTT assay showed concentration-dependent cytotoxicity of nisin towards cancer cell lines, with the IC50 values of 11.5-23 µM, but less toxicity against normal endothelial cells. Furthermore, treatment of cervical cancer cells with 12 µM nisin significantly (P<0.05) increased the Bax/Bcl-2 ratio (4.9-fold), reduced ΔΨm (70%), and elevated ROS levels (1.7-fold). These findings indicated that nisin might have anticancer and apoptogenic activities through mitochondrial dysfunction and oxidative stress damage in cervical cancer cells.

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

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180209152215 ◽

2019 ◽

Vol 18 (9) ◽

pp. 1313-1322 ◽

Cited By ~ 5

Author(s):

Manjula Devi Ramamoorthy ◽

Ashok Kumar ◽

Mahesh Ayyavu ◽

Kannan Narayanan Dhiraviam

Keyword(s):

Prostate Cancer ◽

Reactive Oxygen Species ◽

Cell Cycle ◽

Membrane Potential ◽

Cancer Cells ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Reactive Oxygen ◽

Oxygen Species ◽

Prostate Cancer Cells

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.

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