Diosgenin increases BBC3 expression in HepG2/C3A cells and alters cell communication in a 3D spheroid model

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 bette...

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Published in:Mutation research. Genetic toxicology and environmental mutagenesis 2022-07, Vol.879-880, p.503512-503512, Article 503512
Main Authors: da Silva, Matheus Felipe, de Lima, Luan Vitor Alves, Zanetti, Thalita Alves, Felicidade, Ingrid, Favaron, Phelipe Oliveira, Lepri, Sandra Regina, Lirio Rondina, Débora Berbel, Mantovani, Mário Sérgio
Format: Article
Language:English
Subjects:
3D Culture
DNA damage
Liver cells
Phytochemical
PUMA. Toxicity
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Summary: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. [Display omitted] •Diosgenin induces cell cycle arrest and apoptosis in response to DNA damage.•Diosgenin upregulates of pro-apoptotic gene BBC3.•Diosgenin promotes greater cell breakdown in HepG2/C3A spheroids.
ISSN:1383-5718
1879-3592
DOI:10.1016/j.mrgentox.2022.503512