The cyanobacterial oligopeptides microginins induce DNA damage in the human hepatocellular carcinoma (HepG2) cell line

• Published in: Chemosphere (Oxford) 2020-02, Vol.240, p.124880-124880, Article 124880
• Main Authors: Ujvárosi, Andrea Zsuzsanna, Hercog, Klara, Riba, Milán, Gonda, Sándor, Filipič, Metka, Vasas, Gábor, Žegura, Bojana
• Format: Article
• Language: English
• Subjects: Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Comet Assay; Cyanobacteria - metabolism; Cyanotoxin; DNA damage; DNA Damage - drug effects; DNA Damage - genetics; Genomic Instability; Genotoxic; Hep G2 Cells; Humans; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Microcystis; Microginin; Micronucleus Tests; Oligopeptides; Oligopeptides - pharmacology
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2019.124880

Microginins (MGs) are bioactive metabolites mainly produced by Microcystis spp., (Cyanobacteria) commonly found in eutrophic environments. In this study, the cytotoxic and genotoxic activities of four MG congeners (MG FR3, MG GH787, cyanostatin B, MGL 402) and a well characterized cyanobacterial extract B-14-01 containing these metabolites were evaluated in the human hepatocellular carcinoma (HepG2) cell line. The cytotoxicity was measured with the MTT assay, while genotoxicity was studied with the comet, γH2AX and cytokinesis block (CBMN) micronucleus assays. The viability of cells after 24 h was significantly affected only by the extract, whereas after 72 h a concentration dependent decrease in cell proliferation was observed for the extract and tested microginins, with MGL 402 being the most potent and MG FR3 the least potent congener. The extract and all tested congeners induced DNA strand breaks after 4 and 24 h exposure. The most potent was the extract, which induced concentration and time dependent increase in DNA damage at concentrations ≥0.01 μg mL−1. Among microginins the most potent was MGL 402 (increase in DNA strand breaks at ≥ 0.01 μg mL−1) and MG FR3 was the least potent (increase in DNA strand breaks at ≥ 1 μg mL−1). However, no induction of DNA double strand breaks was observed after 24 and 72-h exposure to the cyanobacterial extract or MGs. Induction of genomic instability was observed in cells exposed to MG GH787, cyanostatin B and the extract B-14-01. This study is the first to provide the evidence that microginins exert genotoxic activity. [Display omitted] •B-14-01 extract reduced viability and proliferation of HepG2 cells.•High concentrations of MGs decreased HepG2 cell proliferation.•B-14-01 extract and MG congeners induced DNA single strand break formation.•B-14-01 extract and MG congeners did not induce DNA double strand breaks.•B-14-01 extract, MG GH787 and cyanostatin B induced genomic instability.