QUERCETIN MEDIATES THE DOWN-REGULATION OF MUTANT P53 IN THE HUMAN BREAST-CANCER CELL-LINE MDA-MB468

The effects of the bioflavonoid quercetin (3,3',4',5,7-pentahydroxyfla vone) on the growth and fell cycle progression of the human breast can cer cell line MDA-MB468 have been studied. Quercetin inhibited cell pr oliferation with an IC50 (a drug concentration which inhibited growth by 50% following a 3-day exposure) value of 7 mu g/ml. In actively gro wing cultures, the addition of quercetin resulted in the accumulation of cells at the G(2)-M phase. We have correlated these effects on cell proliferation with the observation that quercetin strongly inhibited, in a time- and dose-dependent fashion, the expression of the mutated p53 protein, which is the only form present at high levels in this cel l line. This inhibition takes place at the translational level. Querce tin did not affect the steady-state mRNA levels of p53, but prevented the accumulation of newly synthesized p53 protein. This quercetin acti on appeared to be somewhat specific for p53 because the drug did not a lter the amount of other proteins present in MDA-MB468 cells such as P -glycoprotein and did not prevent the induction of the synthesis of ep idermal growth factor receptor in response to epidermal growth factor.