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Apoptosis is a fundamental cellular activity which allows for the maintenance of physiological balance and a protective mechanism against carcinogenesis. Recently, Flavonoids, a broadly distributed class of plant pigments, were known to regulate apoptosis and considerable scientific and therapeutic interest has focused on the structure and functions of these flavonoids in cancer chemotherapy. Despite of the many studies, the pro-oxidant/anti-oxidant properties of flavonoids remain debatable, and the detailed molecular mechanisms of their effects remain largely unknown. The objective, then, of the present work was to assess the apoptosis-modulating effects of several flavonoids in human keratinocyte HaCaT cells. In this study, we treated several flavonoids to human HaCaT keratinocytes and found that 3,4’-dihydroxy flavone and eriodictyol slightly increse cell viability, although other flavonoids including keamferol, quercetin, taxifolin, apigenin, naringenin and isohamnetin showed cell growth inhibition. 3,4’-dihydroxy flavone showed anti-apoptotic effect on etoposide or H2O2-induced cell death. Treatment of cells with 3,4’- dihydroxy flavone has decreased the nuclear fragmentation, PARP or pro-caspase 3 cleavage induced by etoposide or hydrogen peroxide in HaCaT keratinocytes. Taken together, our data strongly suggest that phytochemicals such as flavonoids and etoposide differentially regulate apoptosis in human HaCaT keratinocytes. (Cancer Prev Res 11, 58-64, 2006)