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

Abstract

Nisin, an antimicrobial peptide produced by Lactococcus lactis, is widely used as a safe food preservative and has recently attracted the attention of researchers as a potential anticancer agent. The cytotoxicity of nisin against human cervical cancer cell lines (HeLa), human ovarian carcinoma cell lines (OVCAR-3 and SK-OV-3), and human umbilical vein endothelial cells (HUVECs) was evaluated using an MTT assay. The apoptotic effect of nisin was identified by Annexin-V/propidium iodide assay, which 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 IC50 values of 11.5–23 µM, but less toxicity against normal endothelial cells. Furthermore, the 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 indicate that nisin may have anticancer and apoptogenic activities through mitochondrial dysfunction and oxidative stress damage in cervical cancer cells.