Novel peptide Aurein1.2 derivative induces cytotoxicity in cervical cancer SiHa and HeLa cells by apoptosis and cell cycle arrest.

Cervical cancer remains one of the most common diseases among women worldwide. Although its incidence rate has been on the decline due to widespread vaccination and other preventive measures, significant disparities in prevalence persist across different age groups. Antimicrobial peptides (AMPs) have garnered considerable attention as potential alternative chemotherapeutic agents. The present study aimed to investigate the cytotoxic effect of the Aurein1.2 variant (Aurein1.2 m) on cervical cancer cells and elucidate its underlying mechanism. Results demonstrated that Aurein1.2 m exerted significant cytotoxicity against two cervical cancer cell lines (SiHa and HeLa) while exhibiting relatively low toxicity toward normal cells. Flow cytometry analysis with Annexin V-FITC/PI double staining revealed that Aurein1.2 m induced apoptosis and arrested the cell cycle at the G0/G1 phase in SiHa and HeLa cells. Mechanistically, Aurein1.2 m impaired mitochondrial function by disrupting the mitochondrial membrane potential (Δψm), elevating reactive oxygen species (ROS) levels, and regulating the expression of Bax, Bcl-2, Cleaved caspase 3, and PARP, ultimately leading to mitochondria-dependent apoptosis in SiHa and HeLa cells. Additionally, Aurein1.2 m modulated the expression of CDK4 and Cyclin D1 through inhibiting c-Myc, thereby contributing to G0/G1 phase cell cycle arrest. In vivo experiments showed that Aurein1.2 m effectively suppressed the growth of SiHa-derived tumors without inducing any adverse effects. In conclusion, Aurein1.2 m exerts cytotoxicity against cervical cancer cells by promoting mitochondria-dependent apoptosis and arresting the cell cycle via c-Myc inhibition, highlighting its potential for development as an anti-cervical cancer therapeutic agent.