Li Quanshun, Feng Shirong, Zhang Yuanyuan, Mou Fangyuan, Guo Ting, Qin Baofu, Liu Yihan
College of Life Sciences, Northwest A&F University, Xianyang 712100, China.
College of Chemistry and Pharmacy, Northwest A&F University, Xianyang 712100, China.
Int J Mol Sci. 2024 Dec 6;25(23):13118. doi: 10.3390/ijms252313118.
Steroids are extensively used in the pharmaceutical industry as industrial raw materials for the production of anti-inflammatory and anti-tumor drugs. Microbial transformation, an environmentally friendly method, displays the potential for preparing steroids on an industrial scale. In this study, four steroids, including Diosgenin, Smilagenone, Yamogenin, and 1-Dehydrodiosgenone, were isolated and identified from the solid-state fermentation (SSF) product of a novel strain, and their anti-tumor activities were investigated. The cytotoxicity assay showed that 1-Dehydrodiosgenone had significant inhibitory effects on three tumor cell lines, Hala, A549, and Mad-MB468 cells, with ICs of 6.59 μM, 5.43 μM, and 4.81 μM, respectively. 1-Dehydrodiosgenone significantly induced apoptosis and necrosis of Hala, A549, and Mad-MB468 cells by upregulating the expressions of cleaved caspase-3, cleaved PARP, Bax, and Bad. Moreover, no significant organ damage was observed in mice based on safety tests. Therefore, 1-Dehydrodiosgenone is expected to be developed as a safe and broad-spectrum anti-cancer agent.
类固醇在制药工业中被广泛用作生产抗炎和抗肿瘤药物的工业原料。微生物转化作为一种环境友好型方法，展现出了在工业规模上制备类固醇的潜力。在本研究中，从一株新菌株的固态发酵（SSF）产物中分离并鉴定出了四种类固醇，包括薯蓣皂苷元、剑麻皂苷元、洋地黄皂苷元和1-脱氢薯蓣皂苷元，并对它们的抗肿瘤活性进行了研究。细胞毒性试验表明，1-脱氢薯蓣皂苷元对三种肿瘤细胞系，即哈拉细胞、A549细胞和Mad-MB468细胞具有显著的抑制作用，其IC50分别为6.59 μM、5.43 μM和4.81 μM。1-脱氢薯蓣皂苷元通过上调裂解的半胱天冬酶-3、裂解的聚（ADP-核糖）聚合酶、Bax和Bad的表达，显著诱导哈拉细胞、A549细胞和Mad-MB468细胞凋亡和坏死。此外，基于安全性测试，在小鼠中未观察到明显的器官损伤。因此，1-脱氢薯蓣皂苷元有望被开发成为一种安全的广谱抗癌药物。
