Evaluation of DNA Damage in HepG2 Cells and Mutagenicity of Garcinielliptone FC, A Bioactive Benzophenone

• Published in: Basic & clinical pharmacology & toxicology 2017-06, Vol.120 (6), p.621-627
• Main Authors: Silva Prado, Lismare, Silva, Juliana, Garcia, Ana Letícia Hilario, Boaretto, Fernanda Brião Menezes, Grivicich, Ivana, Conter, Lucas Umpierre, Oliveira Salvi, Aguisson, Reginatto, Flávio Henrique, Vencato, Suele Bierhals, Barros Falcão Ferraz, Alexandre, Picada, Jaqueline Nascimento
• Format: Article
• Language: English
• Subjects: Anticonvulsants; Benzophenone; Bioassays; Biocompatibility; Central nervous system; Colorimetry; Comet assay; Cytokinesis; Cytotoxicity; Damage assessment; Damage detection; DNA Damage; Epilepsy; Genotoxicity; Hep G2 Cells; Hepatoma; Humans; Mammalian cells; Metabolic activation; Metabolic rate; Micronucleus Tests; Mutagenicity; Mutagenicity Tests; Salmonella; Salmonella typhimurium - drug effects; Seeds; Toxicity; Triterpenes - toxicity; Viability
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.12753

Garcinielliptone FC (GFC) is a polyprenylated benzophenone isolated from the hexanic extract of Platonia insignis seeds with potential pharmacological effects on the central nervous system. In a pre‐clinical study, this compound showed anticonvulsant action, becoming a candidate to treat epilepsy disorders. However, genotoxicological aspects of GFC should be known to ensure its safe use. This study investigated the cytotoxic, genotoxic, and mutagenic effects of GFC. Cytotoxicity was evaluated using the colorimetric assay of MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide) in human hepatoma cells (HepG2) (2–100 μg/mL) for 3, 6 and 24 hr. The genotoxic and mutagenic potentials were analysed using the alkaline version of the comet assay, the cytokinesis‐block micronucleus cytome assay in HepG2 cells, and the Salmonella/microsome assay with the strains TA98, TA97a, TA100, TA102 and TA1535, with and without metabolic activation. GFC concentrations above 50 μg/mL were cytotoxic at all experimental times. Viability of HepG2 cells was higher than 70% after exposure to GFC 2–30 μg/mL for 3 hr in the MTT test. No GFC concentration was mutagenic or genotoxic in the Salmonella/microsome and comet assays. Nuclear division index decreased, indicating the cytotoxic effect of the compound, while micronucleus and nuclear bud frequencies rose after treatment with the highest GFC concentration tested (30 μg/mL). Nucleoplasmatic bridges were not observed. The results indicate that GFC is cytotoxic and mutagenic to mammalian cells, pointing to the need for further studies to clarify the toxicological potentials of this benzophenone before proceeding to clinical studies.