Department of General Biology, Center of Biological Sciences, Londrina State University, UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380 Londrina, PR, Brazil.
Department of General Biology, Center of Biological Sciences, Londrina State University, UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380 Londrina, PR, Brazil.
Mutat Res Genet Toxicol Environ Mutagen. 2022 Jul-Aug;879-880:503512. doi: 10.1016/j.mrgentox.2022.503512. Epub 2022 Jun 12.
Preclinical studies have shown that diosgenin, a steroidal sapogenin, is a promising phytochemical for treating different pathological conditions, such as cancer, diabetes, and cardiovascular diseases. However, the toxicological safety of this molecule for therapeutic use in humans needs to be better understood. Thus, this study aimed to evaluate the mechanisms of action of diosgenin in HepG2/C3A human hepatocellular carcinoma cells. Cytotoxicity, genotoxicity, alterations in the cell cycle, and cell death (apoptosis) were investigated and associated with the gene expression profile of pathways involved in these processes. The effects of diosgenin on the growth of spheroids were also tested. Diosgenin induced a dose-dependent reduction in cell viability and cell cycle arrest in S and G/M phases and apoptosis in response to DNA damage. Apoptosis was associated with an increase in the expression of BBC3, a participant in the intrinsic apoptosis pathway. Diosgenin also promoted an increase in volume and greater cellular breakdown in spheroids. These results allowed a better understanding of the toxicity of diosgenin in human cells and contributed to the development of treatments based on this phytochemical.
临床前研究表明，薯蓣皂素是一种甾体皂素，作为一种有前途的植物化学物质，可用于治疗多种病理状况，如癌症、糖尿病和心血管疾病。然而，为了将该分子用于人类治疗，需要更好地了解其毒理学安全性。因此，本研究旨在评估薯蓣皂素在 HepG2/C3A 人肝癌细胞中的作用机制。研究了细胞毒性、遗传毒性、细胞周期改变和细胞死亡（细胞凋亡），并将其与涉及这些过程的途径的基因表达谱相关联。还测试了薯蓣皂素对球体生长的影响。薯蓣皂素诱导细胞活力呈剂量依赖性降低，S 和 G/M 期细胞周期停滞，并通过 DNA 损伤诱导细胞凋亡。凋亡与内在凋亡途径参与者 BBC3 的表达增加有关。薯蓣皂素还促进了球体体积增加和细胞分解加剧。这些结果使我们更好地了解了薯蓣皂素对人细胞的毒性，并为基于这种植物化学物质的治疗方法的开发做出了贡献。
