Quercetin Prevents Hydrogen Peroxide-induced Necrotic and Apoptotic Cell Death in Human Colonic Epithelial Cells
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Abstract
Quercetin is one of the most distributed flavonoids in the plant kingdom and occurs naturally in a wide range of fruits and vegetables. This study was undertaken to determine whether quercetin exerts beneficial effect against necrotic and apoptotic cell death induced by hydrogen peroxide (H2O2) in intestinal cells using the human-derived cultured T84 colonic epithelial cell line. Necrotic cell death was induced by exposing cells to 0.5 mM H2O2 for 2 h and apoptosis was induced by incubating cells in normal culture medium for 18 h following exposure of cells to 0.5 mM H2O2 for 2 h. Cell viability was evaluated by the trypan blue exclusion assay and apoptosis was assessed by Hoechst 33258 staining and flow cytometry. H2O2 induced necrotic cell death in a time and dose-dependent fashion. Both necrotic and apoptotic cell deaths were not prevented by the antioxidants N,N’-diphenyl-p-phenylenediamine(DPPD) and Trolox, whereas both cell deaths induced by the organic hydroperoxide t-butylhydroperoxide (tBHP) were prevented by DPPD, suggesting that H2O2 induces cell death through a lipid peroxidation-independent mechanism. H2O2-induced necrotic death was prevented by deferoxamine and 3-aminobenzamide, while the apoptotic cell death was not affected by these agents. Quercetin prevented both necrotic and apoptotic cell deaths induced by H2O2 in a dose-dependent manner. H2O2 caused activation of poly (ADP-ribose) polmerase (PARP), which was inhibited by deferoxamine, 3-aminobenzamide, and quercetin, but not DPPD. These results indicate that quercetin inhibits both necroticand apoptotic deaths of T84 cells. The anti-necrotic effect of quercetin may be attributed to its iron chelator activity rather than a direct H2O2 scavenging capacity and antioxidant. The present study suggests that quercetin may play a therapeutic role in the treatment of human gastrointestinal diseases mediated by oxidants.
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