title: Diosmin induces genotoxicity and apoptosis in DU145 prostate cancer cell line.
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.
authors.affiliation: Department of Biochemistry and Cell Biology, University of Rzeszow, Zelwerowicza 4, 35-601 Rzeszow, Poland. Electronic address: alewinska@o2.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Lewinska
authors.affiliation: Department of Genetics, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Siwak
authors.affiliation: Department of Genetics, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Rzeszutek
authors.affiliation: Department of Genetics, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Wnuk
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001973:Bromodeoxyuridine; D045744:Cell Line, Tumor; D020552:Comet Assay; D019175:DNA Methylation / Q000187:drug effects; D004145:Diosmin / Q000633:toxicity*; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000473:pathology; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D009153:Mutagens; D013778:Tetrazolium Salts; D013844:Thiazoles; D004145:Diosmin; C022616:thiazolyl blue; D001973:Bromodeoxyuridine
keywords: Apoptosis; Cancer cells; DNA methylation; Flavonoid glycosides; Genotoxicity