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

Autor(es)

Ribeiro, Arthur B. ^[1] ; Ozelin, Saulo D. ^[1] ; da Silva, Lucas H. D. ^[1] ; Rinaldi-Neto, Francisco ^[1] ; Freitas, Karoline S. ^[1] ; Nicolella, Heloiza D. ^[1] ; de Souza, Larissa D. R. ^[1] ; Furtado, Ricardo A. ^[1] ; Cunha, Wilson Roberto ^[1] ; Tavares, Denise C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Franca, Lab Mutagenese, Ave Dr Armando Salles Oliveira 201, BR-14404600 Franca, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY; v. 35, n. 4 JAN 2021.
• Citações Web of Science: 1

Resumo

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 IC50 values ranging from 13.91 to 111.72 mu M. In the case of M059J, AA exhibited selective cytotoxicity after 48 h of treatment (IC50 = 24 mu M), 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 mu M), revealing genotoxic activity. In contrast, low concentrations (5, 10, and 20 mu M) 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 mu M). 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. (AU)

• Processo FAPESP: 16/24269-7 - Análise dos efeitos do manool, um diterpeno da Salvia officinalis, sobre a integridade celular e genômica
• Beneficiário: Denise Crispim Tavares
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/21068-0 - Estudo toxicogenético do ácido asiático e de sua influência sobre a instabilidade genômica
• Beneficiário: Arthur Barcelos Ribeiro
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica