Antibacterial Peptide Nisin Activates <scp>p53</scp> Gene Expression and Triggers Apoptosis in Human Colon Cancer Cells

ABSTRACT Antimicrobial peptides (AMPs) are renowned for their broad‐spectrum efficacy against viruses, bacteria, and fungi, thereby holding promise for medicinal applications. Nisin, a bacteriocin synthesized by gram‐positive bacteria such as Lactobacillus and Streptococcus , has been used as a food preservative owing to its antimicrobial characteristics for decades. However, recent developments prompt further research on its application as therapeutic interventions, mainly focusing on anticancer activity. In line with this, the present study portrays the effects of nisin on human colorectal cancer cells and the underlying molecular mechanisms. A dose‐dependent decrease in cell viability with increasing concentrations of nisin was determined by the Alamar blue viability assay, which was supported by significant morphological changes in cells. Subsequently, we probed the apoptotic effects of nisin using EtBr/AO staining, confirming the induction of apoptosis upon nisin treatment, which was further confirmed by ELISA analysis. Elevated levels of Caspase 7 indicated increased apoptosis in nisin‐treated cells. As pharmaceutical p53 reactivation is considered as an attractive strategy to combat chemoresistance and adverse effects, the effect of nisin on p53 expression was determined by mRNA analysis. An upregulation in p53 expression in nisin‐treated cells compared to untreated controls suggests that bacterial nisin reactivates mutated p53. To assess cell cycle dynamics, we utilized PI flow cytometry, unveiling a G0/G1 phase arrest in nisin‐treated cells in contrast to untreated controls. In summary, our results strongly advocate the potential of nisin as a compelling candidate for drug development against colorectal cancer.