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Aneugenic effects of the genistein glycosidic derivative substituted at C7 with the unsaturated disaccharide

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Abstract

Genistein, due to its recognized chemopreventive and antitumour potential, is a molecule of interest as a lead compound in drug design. Recently, we found that the novel genistein derivative, [7-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-(1 → 4)-(6-O-acetyl-hex-2-ene-α-D-erythro pyranosyl)genistein, named G21, induced aberrations in mitotic spindle formation. In the presented study, we investigated the properties of G21 relevant to its genotoxic activity. The inhibition of topoisomerase IIα activity was evaluated in decatenation assay and immunoband depletion assay, the covalent DNA–topoisomerase IIα complexes and histone ɣH2AX were detected immunofluorescently. Genotoxic effects of the tested compounds were assessed in micronucleation assay. The presence of centromeres in the micronuclei and the multiplication of centrosomes were evaluated in fluorescence immunolabelled specimens. The inhibition of tubulin polymerization was measured spectrophotometrically. We found that both tested drugs were able to inhibit topoisomerase II activity; however, G21, in contrast to genistein, blocked this enzyme at the concentration far exceeding cytotoxic IC50. We also found that both compounds caused micronucleation in DU 145 prostate cancer cells, but in contrast to genistein, G21 exhibited aneugenic activity, manifested by the presence of centromeres in micronuclei formed in cells treated with the drug. Aneugenic properties of G21 resulted from the inhibition of tubulin polymerization and centrosome disruption, not observed in the presence of genistein. The study supports and extends our previous observations that the mechanisms of cytotoxicity of genistein and its new glycosidic derivative—G21 are significantly different.

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Acknowledgements

This work was supported by Grant of Foundation for Supporting of Polish Pharmacy and Medicine 06/FB/2004 and PBZ MNiI-1/1/2005. AG-P was supported by the Regional Graduate Studies Fund within the framework of the Integrated Regional Operational Programme financed by the European Social Fund.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Center For Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland, Wybrzeże Armii Krajowej 15, 44-101, Gliwice, Poland

    Agnieszka Gogler-Pigłowska, Aleksandra Rusin, Daria Bochenek & Zdzisław Krawczyk

  2. Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, Krzywoustego 4, 44-100, Gliwice, Poland

    Zdzisław Krawczyk

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  1. Agnieszka Gogler-Pigłowska
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  2. Aleksandra Rusin
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  4. Zdzisław Krawczyk
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Correspondence to Aleksandra Rusin.

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Gogler-Pigłowska, A., Rusin, A., Bochenek, D. et al. Aneugenic effects of the genistein glycosidic derivative substituted at C7 with the unsaturated disaccharide. Cell Biol Toxicol 28, 331–342 (2012). https://doi.org/10.1007/s10565-012-9227-9

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