Quercetin apoptotic effect

Certain natural compounds possess anti-apoptotic effects. For example, ascorbic acid and a-tocopherol prevent apoptosis caused by serum withdrawal in HL-60 cells with the antioxidative effects (76). Caffeic acid inhibits ceramide-induced apoptosis in U937 cells through the inhibition of protein tyrosine kinase activity 17). Quercetin inhibits hydrogen peroxide-induced apoptosis via intervention in the activator protein 1 (AP-1) -mediated apoptotic pathway 18). Epigallocatechin-3-gallate and theaflavins inhibits arsenite-induced apoptosis through the decrease in phosphorylation of Erks and JNKs (79). Therefore, it is important to know whether these natural compounds show inhibitory effects on Trp-P-1-induced apoptosis. In this study, we demonstrated that Trp-P-1 induced caspase-8-initiated apoptosis in rat MNCs, and that certain food components inhibited Trp-P-l-induced apoptosis. 

In U-937 leukemia cells and mice harboring xenografts of this cell line, the proapoptotic effects of quercetin resulted in both the increased expression of the proapoptotic factor Bax and the inhibition of anti-apoptotic Mcl-l [291]. Quercetin causes apoptosis in both transformed and primary leukemia cells but not in normal blood peripheral mononuclear cells at concentrations up to 50 mM [292]. Further, quercetin has been shown to be a potent enhancer of TRAIL-induced apoptosis in prostate and hepatocellular carcinoma cells [293, 294]. 

The predominant effect of flavonoid and isoflavonoid supplementation in ex vivo cell culture models appears to be one of promoting apoptosis [54—57]. This is repeatedly observed in studies witti transformed cancer cells, leading to the descriptions cytoprotective and/or chemopreventive [6,58]. Two poly-phenolic compounds that have been extensively studied in anticancer research are quercetin and genistein, a flavonoid and isoflavone, respectively. However, ex vivo studies with primary cultured cells in 2000 and 2001 showed that some flavonoids can prevent apoptosis promoted by agents that induce oxidative stress [7,8,59]. The outcome of flavonoid treatment is expected to show a complex dependence on a number of factors, including the type of flavonoid, its concentration, the type of cell (e.g., transformed versus nontransformed), the mechanisms of action of the flavonoid, the nature of the proapoptotic stimulus, and the specific apoptotic signaling pathway that is activated. 

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