First study to show that microginins are genotoxic

Abstract from a paper by Ujvarosi et al. (2019), published in Chemospere :

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.

The paper is a product of joined research by groups in Slovenia and Hungary and features CYANOCOST members Bojana Zegura, Gabor Vasas, Klara Hercog, Metka Filipic. The authors acknowledge CYANOCOST.

Reference:

Andrea Zsuzsanna Ujvárosi, Klara Hercog, Milán Riba, Sándor Gonda, Metka Filipič, Gábor Vasas, Bojana Žegura (2019). “The cyanobacterial oligopeptides microginins induce DNA damage in the human hepatocellular carcinoma (HepG2) cell line”, Chemosphere, Volume 240,  https://doi.org/10.1016/j.chemosphere.2019.124880.

 

Microginins from a Microcystis sp. Bloom Material Collected from the Kishon Reservoir, Israel

From the abstract of a recent paper by Anat Lodin-Friedman and Shmuel Carmeli, published in Marine Drugs:

“During blooms, cyanobacteria produce diverse modified peptides. Among these are the microginins, which inhibit zinc-containing metalloproteases. Ten microginins, microginins KR767 (1), KR801(2), KR835 (3), KR785 (4), KR604 (5), KR638 (6), KR781 (7), KR815 (8), FR3 (9), and FR4 (10), were isolated from the extract of a bloom material of Microcystis sp. (IL-405) collected from the Kishon Reservoir, Israel in the fall of 2009. The structures of the pure compounds were elucidated using 1D and 2D NMR techniques and high-resolution mass spectrometry. The absolute configuration of the chiral centers of the amino acids were determined by Marfey’s and advance Marfey’s methods and by comparison of 1H and 13C NMR chemical shifts of the Ahda derivatives with those of known microginins. These microginins differ in sequence and absolute configuration of the chiral centers of the Ahda moieties and by N-methylation of the Ahda amine group and extent of chlorination of the Ahda terminal methyl group. The compounds were evaluated for inhibition of the zinc metalloprotease, aminopeptidase M, and exhibited low- to sub-nanomolar half maximal inhibitory concentration (IC50) values”.

Reference:

Lodin-Friedman, A.; Carmeli, S. Microginins from a Microcystis sp. Bloom Material Collected from the Kishon Reservoir, Israel. Mar. Drugs 2018, 16, 78. https://doi.org/10.3390/md16030078