Mycosubtilin Induces G1 Phase Block and Autophagy in Cervical Cancer HeLa Cells

Cyclic lipopeptides secreted by the probiotic bacterium Bacillus subtilis have attracted much attention due to their antitumor activities and low toxicity. However, the role of Mycosubtilin (Myco) in the prevention and treatment of cervical cancer remains unclear. In the present study, we conducted a systematic evaluation of Myco’s anti-cervical cancer effects to identify its molecular mechanism of action using proteomics technology. The results reveal that Myco inhibited the growth of HeLa and SiHa cervical cancer cell lines in a dose-dependent (3–15 µg/mL) and time-dependent (12–48 h) manner and significantly reduced colony formation and migration in HeLa cells, highlighting its potential to suppress tumor spread. Moreover, autophagosome and autolysosome numbers were significantly increased after Myco treatment, and the expression of autophagy-related proteins was significantly modulated, suggesting that autophagy plays a role in its anti-cancer mechanism. Myco treatment also induced G1 phase cell cycle arrest in HeLa cells, as confirmed by proteomics analysis. Myco was shown to induce cell cycle arrest in HeLa cells by regulating the P53 pathway and autophagy-dependent cell death via the PI3K/AKT/mTOR signaling pathway, demonstrating its multidimensional effect on cervical cancer cell growths. Myco treatment significantly inhibited tumor growth in vivo in a nude mouse cervical cancer xenograft model, providing direct evidence of its potential as a therapeutic candidate for cervical cancer. Given its unique anti-cancer mechanism and significant therapeutic efficacy, Myco should be considered a promising therapeutic agent for cervical cancer.