Influence of Asiatic acid on cell proliferation and DNA damage in vitro and in vivo systems.

Autor: Ribeiro AB; Laboratório de Mutagênese, Universidade de Franca, Franca, São Paulo, Brazil., Ozelin SD; Laboratório de Mutagênese, Universidade de Franca, Franca, São Paulo, Brazil., da Silva LHD; Laboratório de Mutagênese, Universidade de Franca, Franca, São Paulo, Brazil., Rinaldi-Neto F; Laboratório de Mutagênese, Universidade de Franca, Franca, São Paulo, Brazil., Freitas KS; Laboratório de Mutagênese, Universidade de Franca, Franca, São Paulo, Brazil., Nicolella HD; Laboratório de Mutagênese, Universidade de Franca, Franca, São Paulo, Brazil., de Souza LDR; Laboratório de Mutagênese, Universidade de Franca, Franca, São Paulo, Brazil., Furtado RA; Laboratório de Mutagênese, Universidade de Franca, Franca, São Paulo, Brazil., Cunha WR; Laboratório de Mutagênese, Universidade de Franca, Franca, São Paulo, Brazil., Tavares DC; Laboratório de Mutagênese, Universidade de Franca, Franca, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2021 Apr; Vol. 35 (4), pp. e22712. Date of Electronic Publication: 2021 Jan 23.
DOI: 10.1002/jbt.22712
Abstrakt: Asiatic acid (AA) is a triterpene with promising pharmacological activity. In the present study, in vitro and in vivo assays were conducted to understand the effect of AA on cell proliferation and genomic instability. AA was cytotoxic to human tumor cell lines (M059J, HeLa, and MCF-7), with IC 50 values ranging from 13.91 to 111.72 µM. In the case of M059J, AA exhibited selective cytotoxicity after 48 h of treatment (IC 50  = 24 µM), decreasing the percentage of cells in the G0/G1 phase, increasing the percentage of cells in the S phase, and inducing apoptosis. A significant increase in chromosomal damage was observed in V79 cell cultures treated with AA (40 µM), revealing genotoxic activity. In contrast, low concentrations (5, 10, and 20 µM) of AA significantly reduced the frequencies of micronuclei induced by the mutagens doxorubicin (DXR), methyl methanesulfonate, and hydrogen peroxide. A reduction of DXR-induced intracellular free radicals was found in V79 cells treated with AA (10 µM). The antigenotoxic effect of AA (30 mg/kg) was also observed against DXR-induced chromosomal damage in Swiss mice. Significant reductions in p53 levels were verified in the liver tissue of these animals. Taken together, the data indicate that AA exerted antiproliferative activity in M059J tumor cells, which is probably related to the induction of DNA damage, leading to cell cycle arrest and apoptosis. Additionally, low concentrations of AA exhibited antigenotoxic effects and its antioxidant activity may be responsible, at least in part, for chemoprevention.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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