Novel peptide Aurein1.2 derivative regulates the cell cycle and apoptosis via the P53 pathway in prostate cancer
Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men, and drug resistance severely hinders effective treatment and the improvement of patient survival rates. Aurein1.2m is an optimized mutant derived from the Australian frog skin antimicrobial peptide Aurein1.2, featuring enhanced cell membrane lytic activity and significant anti-tumor potential. This study aimed to elucidate its anti-prostate cancer mechanisms.In vitro experiments evaluated the effects of Aurein1.2m on prostate cancer cells, including cytotoxicity induction, cell cycle arrest, apoptosis promotion, oxidative stress triggering, mitochondrial damage, and ferroptosis induction. To investigate the transcriptomic effects of Aurein1.2m on PC-3 prostate cancer cells, we collected three biological replicates of both untreated control PC-3 cells and PC-3 cells treated with Aurein1.2m for 24 hours, followed by RNA-seq analysis. Transcriptomic analysis (RNA-seq), combined with Western blotting and RT-qPCR validation, revealed that Aurein1.2m regulates cell apoptosis and cycle progression via the P53 signaling pathway. Additionally, the in vivo anti-tumor efficacy and safety of Aurein1.2m were confirmed using a prostate cancer mouse xenograft model.The results demonstrated that Aurein1.2m exerts potent anti-prostate cancer effects through a multimodal mechanism: it disrupts the cell membrane to penetrate cells, induces mitochondrial damage and ferroptosis, and mediates cell cycle arrest and apoptosis via the P53 pathway. Moreover, it effectively inhibits tumor growth in vivo with favorable safety profiles.