枯草芽孢杆菌产生的脂肽具有抗癌潜力。我们之前鉴定了枯草芽孢杆菌Z15菌株（BS-Z15）的次级代谢产物，该菌株具有调节脂肽合成的操纵子，并证明该菌株的发酵产物具有抗氧化和促免疫作用。本研究的目的是在体外和体内研究 BS-Z15 次级代谢产物（BS-Z15 SM）对肝细胞癌细胞（HCC）的抗癌作用。 BS-Z15 SM 显着抑制 H22 细胞来源的小鼠异种移植肿瘤生长，且没有任何全身毒性。此外，BS-Z15 SM 在体外降低了 H22 细胞和 BEL-7404 细胞的活力，IC50 值分别为 33.83 和 27.26 µg/mL。与此一致的是，BS-Z15 SMs 诱导 BEL-7404 细胞凋亡和 G0/G1 期阻滞，线粒体膜电位也以剂量依赖性方式显着降低。从机制上讲，BS-Z15 SM 上调促凋亡 p53、Bax、细胞色素 C 和 cleaved-caspase-3/9 蛋白，并下调抗凋亡 Bcl-2。这些发现表明BS-Z15 SMs诱导HCC细胞凋亡可能与线粒体途径有关。因此，枯草芽孢杆菌菌株 Z15 的次级代谢产物有望成为临床治疗肝癌的新型抗癌药物。© 2023。作者获得 Springer Science Business Media, LLC 的独家许可，该公司是施普林格自然。

The lipopeptides produced by Bacillus subtilis have anti-cancer potential. We had previously identified a secondary metabolite of B. subtilis strain Z15 (BS-Z15), which has an operon that regulates lipopeptide synthesis, and also demonstrated that the fermentation products of this strain exerted antioxidant and pro-immune effects. The purpose of this study was to investigate in vitro and in vivo the anticancer effects of BS-Z15 secondary metabolites (BS-Z15 SMs) on hepatocellular carcinoma (HCC) cells. BS-Z15 SMs significantly inhibited H22 cell-derived murine xenograft tumor growth without any systemic toxicity. In addition, BS-Z15 SMs decreased the viability of H22 cells and BEL-7404 cells in vitro with respective IC50 values of 33.83 and 27.26 µg/mL. Consistent with this, BS-Z15 SMs induced apoptosis and G0/G1 phase arrest in the BEL-7404 cells, and the mitochondrial membrane potential was also significantly reduced in a dose-dependent manner. Mechanistically, BS-Z15 SMs upregulated the pro-apoptotic p53, Bax, cytochrome C, and cleaved-caspase-3/9 proteins and downregulated the anti-apoptotic Bcl-2. These findings suggest that the induction of apoptosis in HCC cells by BS-Z15 SMs may be related to the mitochondrial pathway. Thus, the secondary metabolites of B. subtilis strain Z15 are promising to become new anti-cancer drugs for the clinical treatment of liver cancer.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.