Toxicology in Vitro 2015-04-01

Diosmin induces genotoxicity and apoptosis in DU145 prostate cancer cell line.

Anna Lewinska, Justyna Siwak, Iwona Rzeszutek, Maciej Wnuk

Index: Toxicol. In Vitro 29(3) , 417-25, (2015)

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Abstract

Plant-derived dietary polyphenolic compounds, such as flavonoids, with cancer cell-specific pro-apoptotic activity and chemopreventive potential are thought to be promising anticancer agents. In the present study, we were interested in determining if flavonoid-induced genotoxicity may also provoke cancer cell death. Cyto- and genotoxicity of three selected flavonoid glycosides (naringin, diosmin and hesperidin) in DU145 prostate cancer cell line were investigated. Flavonoid glycosides decreased cancer cell number and proliferative activity in a different manner. Flavonoid glycosides induced oxidative stress: intracellular total ROS and superoxide production were augmented after flavonoid treatment. Flavonoid glycosides stimulated DNA double strand breaks (DSBs) and micronuclei production. Diosmin was found the most potent genotoxic agent in DU145 cells, which, in turn, resulted in its pro-apoptotic activity. The more robust recruitment of 53BP1 was correlated with lower DNA and chromosomal damage after naringin and hesperidin treatment compared with diosmin treatment. Flavonoid glycosides were also found to be DNA hypomethylating agents with an ability to modulate cancer cell epigenome leading to changes in the gene expression patterns. Taken together, diosmin, a dietary flavonoid glycoside, was found active against DU145 cells by promoting genotoxic events and a concomitant apoptotic cell death. Thus, a comprehensive analysis of biological activity of diosmin against cancer cells both in vitro and in vivo deserves further investigation. Copyright © 2014 Elsevier Ltd. All rights reserved.