Consumption of fruits and vegetables has been associated with cancer prevention; flavonoids are widely distributed in plant foods and considered to be the active ingredients. Quercetin and kaempferol are two of the most commonly found dietary flavonols, and have been reported to prevent cancer. We have previously reported that the isoflavone genistein and the flavone baicalein exert differential actions on the oestrogen receptor (OR) a in HepG2 cells. Because of the structural resemblance to both isoflavone and flavone, we examined the effects of these dietary flavonols on ORa -and ORb -specific transactivations and their subsequent involvement in inducing MCF-7 cell death. In the present study, both quercetin and kaempferol were able to compete for OR binding in a cell-free system and were agonistic to ORa and -b expressed in HepG2 cells, while some additive effect was observed in the oestrogen response element (ORE)-driven transcription when 17b-oestradiol was co-administered. Since the bcl-2 promoter contained two ORE, and ORE-driven transcriptional activity and Bcl-2 mRNA expression were increased by treatment with 10 mM-quercetin or kaempferol, it is possible that quercetin and kaempferol might up-regulate Bcl-2 expression through OR transactivation in MCF-7 cells. Cell death ELISA assay performed on MCF-7 cells indicated that an increase of apoptosis occurred at 25 mM-, but not 10 mM-, quercetin or kaempferol. Indirectly the results suggest that OR activation is not sufficient to induce apoptosis and that apoptosis is induced despite an increase in Bcl-2 expression.
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