Assessment of the chemopreventive effect of casearin B, a clerodane diterpene extracted from Casearia sylvestris (Salicaceae)

• Autor(a) principal: Prieto, Aline M. [UNESP]
• Data de Publicação: 2013
• Outros Autores: Santos, André Gonzaga dos [UNESP], Oliveira, Ana Paula S. [UNESP], Cavalheiro, Alberto José [UNESP], Silva, Dulce H.S. [UNESP], Bolzani, Vanderlan da Silva [UNESP], Varanda, Eliana Aparecida [UNESP], Soares, Christiane P. [UNESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1016/j.fct.2012.11.029; http://hdl.handle.net/11449/74660
• topic: Ames test; Antioxidant; Casearia sylvestris; Casearin B; Comet assay; DCFDA; casearin b; hydrogen peroxide; plant extract; reactive oxygen metabolite; unclassified drug; antigenotoxicity; antioxidant activity; Casearia; cell viability; chemoprophylaxis; comet assay; concentration response; controlled study; DNA damage; drug activity; drug efficacy; drug mechanism; drug structure; genotoxicity; human; human cell; IC 50; mutation inhibition; Aflatoxin B1; Antimutagenic Agents; Antioxidants; Chemoprevention; Comet Assay; Diterpenes; Diterpenes, Clerodane; DNA Damage; DNA-Formamidopyrimidine Glycosylase; Dose-Response Relationship, Drug; Hep G2 Cells; Humans; Hydrogen Peroxide; Mutagens; Plant Extracts; Reactive Oxygen Species; Salicaceae

Studies have shown that Casearia sylvestris compounds protect DNA from damage both in vitro and in vivo. Complementarily, the aim of the present study was to assess the chemopreventive effect of casearin B (CASB) against DNA damage using the Ames test, the comet assay and the DCFDA antioxidant assay. The genotoxicity was assessed by the comet assay in HepG2 cells. CASB was genotoxic at concentrations higher than 0.30μM when incubated with the FPG (formamidopyrimidine-DNA glycosylase) enzyme. For the antigenotoxicity comet assay, CASB protected the DNA from damage caused by H2O2 in the HepG2 cell line in concentrations above 0.04μM with post-treatment, and above 0.08μM with pre-treatment. CASB was not mutagenic (Ames test) in TA 98 and TA 102. In the antimutagenicity assays, the compound was a strong inhibitor against aflatoxin B1 (AFB) in TA 98 (>88.8%), whereas it was moderate (42.7-59.4%) inhibitor against mytomicin C (MMC) in TA 102. Additionally, in the antioxidant assay using DCFDA, CASB reduced reactive oxygen species (ROS) generated by H2O2. In conclusion, CASB was genotoxic to HepG2 cells at high concentrations; was protective of DNA at low concentrations, as shown by the Ames test and comet assay; and was also antioxidant. © 2012 Elsevier Ltd.