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.
Subject(s)
Apoptosis/drug effects , Diosmin/toxicity , Mutagens/toxicity , Bromodeoxyuridine , Cell Line, Tumor , Comet Assay , DNA Methylation/drug effects , Humans , Male , Membrane Potential, Mitochondrial/drug effects , Micronucleus Tests , Oxidative Stress/drug effects , Prostatic Neoplasms/pathology , Tetrazolium Salts , ThiazolesABSTRACT
Plant polyphenols, such as flavonoids, are ubiquitous components of human diet, and have been recognised as efficient radical scavengers and antioxidants. Their protective effects were especially seen in cell-free assays. Whilst in living cells, depending on experimental conditions, polyphenols may manifest both anti- and pro-oxidative activity. In the present study, the effectiveness of fifteen structurally different flavonoids against hypochlorite-mediated changes in in vitro systems, with and without cells, was tested and compared. Quercetin was found to be the best protector against hypochlorite-mediated fluorescein bleaching and BSA thiol groups oxidation, whilst in living cells its effects on hypochlorite-associated cytotoxicity were moderate. Contrary, epigallocatechin gallate, pelargonidin and catechin, with less impressive hypochlorite scavenging activity in cell-free assays, were the most effective against 3-chlorotyrosine formation after hypochlorite treatment. Taken together, special care should be taken when extrapolating the results on antioxidant propensity of food bioactive compounds in vitro to the cellular milieu.
