期刊
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
卷 879-880, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.mrgentox.2022.503512
关键词
3DCulture; DNAdamage; Livercells; Phytochemical; PUMA.Toxicity
This study aimed to evaluate the mechanisms of action of diosgenin in human hepatocellular carcinoma cells. The results showed that diosgenin induced cell cycle arrest and apoptosis through DNA damage, leading to reduced cell viability and inhibited growth of spheroids.
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 G2/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.
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