Betulinic acid exerts antigenotoxic and anticarcinogenic activities via inhibition of COX-2 and PCNA in rodents.

Autor: Ferreira NH; Mutagenesis Laboratory and Organic Chemistry Laboratory, University of Franca, Franca, São Paulo, Brazil., Cunha NL; Mutagenesis Laboratory and Organic Chemistry Laboratory, University of Franca, Franca, São Paulo, Brazil., de Melo MRS; Mutagenesis Laboratory and Organic Chemistry Laboratory, University of Franca, Franca, São Paulo, Brazil., Fernandes FS; Mutagenesis Laboratory and Organic Chemistry Laboratory, University of Franca, Franca, São Paulo, Brazil., de Freitas KS; Mutagenesis Laboratory and Organic Chemistry Laboratory, University of Franca, Franca, São Paulo, Brazil., do Nascimento S; Mutagenesis Laboratory and Organic Chemistry Laboratory, University of Franca, Franca, São Paulo, Brazil., Ribeiro AB; Mutagenesis Laboratory and Organic Chemistry Laboratory, University of Franca, Franca, São Paulo, Brazil., de A E Silva ML; Mutagenesis Laboratory and Organic Chemistry Laboratory, University of Franca, Franca, São Paulo, Brazil., Cunha WR; Mutagenesis Laboratory and Organic Chemistry Laboratory, University of Franca, Franca, São Paulo, Brazil., Tavares DC; Mutagenesis Laboratory and Organic Chemistry Laboratory, University of Franca, Franca, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2021 Dec; Vol. 35 (12), pp. e22917. Date of Electronic Publication: 2021 Sep 19.
DOI: 10.1002/jbt.22917
Abstrakt: Phytochemicals have been suggested as an effective strategy for cancer prevention. Within this context, triterpene betulinic acid (BA) exhibits several biological properties but its chemopreventive effect has not been fully demonstrated. The present study investigated the antigenotoxic potential of BA against doxorubicin (DXR)-induced genotoxicity using the mouse peripheral blood micronucleus assay, as well as its anticarcinogenic activity against 1,2dimethylhydrazine (DMH)-induced colorectal lesions in rats. Micronuclei (MN) assay and aberrant crypt foci assay were used to assess the antigenotoxic and the anticarcinogenic potential, respectively. The molecular mechanisms underlying the anticarcinogenic activity of BA were evaluated by assessing anti-inflammatory (COX-2) and antiproliferative (PCNA) pathways. The results demonstrated that BA at the dose of 0.5 mg/kg bodyweight exerted antigenotoxic effects against DXR, with a reduction of 70.2% in the frequencies of chromosomal damage. Animals treated with BA showed a 64% reduction in the number of preneoplastic lesions when compared to those treated with the carcinogen alone. The levels of COX-2 and PCNA expression in the colon were significantly lower in animals treated with BA and DMH compared to those treated with the carcinogen alone. The chemopreventive effect of BA is related, at least in part, to its antiproliferative and anti-inflammatory activity, indicating a promising potential of this triterpene in anticancer therapies, especially for colorectal cancer.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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