title: Assessment of the chemopreventive effect of casearin B, a clerodane diterpene extracted from Casearia sylvestris (Salicaceae).
abstract: 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 0.30 μM when incubated with the FPG (formamidopyrimidine-DNA glycosylase) enzyme. For the antigenotoxicity comet assay, CASB protected the DNA from damage caused by H(2)O(2) in the HepG2 cell line in concentrations above 0.04 μM with post-treatment, and above 0.08 μM 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 H(2)O(2). 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.
authors.affiliation: UNESP-Univ. Estadual Paulista, Araraquara, School of Pharmaceutical Sciences, Department of Clinical Analysis, Rua Expedicionários do Brasil 1621, Araraquara, SP, Brazil.
authors.forename: Aline M
authors.initials: AM
authors.lastname: Prieto
authors.forename: André G
authors.initials: AG
authors.lastname: dos Santos
authors.forename: Ana Paula S
authors.initials: AP
authors.lastname: Oliveira
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Cavalheiro
authors.forename: Dulce H S
authors.initials: DH
authors.lastname: Silva
authors.forename: Vanderlan S
authors.initials: VS
authors.lastname: Bolzani
authors.forename: Eliana Ap
authors.initials: EA
authors.lastname: Varanda
authors.forename: Christiane P
authors.initials: CP
authors.lastname: Soares
mesh_terms: D016604:Aflatoxin B1 / Q000378:metabolism / Q000633:toxicity; D016587:Antimutagenic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D037821:Casearia / Q000737:chemistry*; D018890:Chemoprevention; D020552:Comet Assay / Q000379:methods; D004249:DNA Damage / Q000187:drug effects; D043382:DNA-Formamidopyrimidine Glycosylase / Q000235:genetics / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D045785:Diterpenes, Clerodane / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects; D009153:Mutagens / Q000009:adverse effects; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016587:Antimutagenic Agents; D000975:Antioxidants; D004224:Diterpenes; D045785:Diterpenes, Clerodane; D009153:Mutagens; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C582885:casearin B; D016604:Aflatoxin B1; D006861:Hydrogen Peroxide; D043382:DNA-Formamidopyrimidine Glycosylase