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-pentahydroxyflavone) on the growth and cell cycle progression of the human breast cancer cell line MDA-MB468 have been studied. Quercetin inhibited cell proliferation with an IC50 (a drug concentration which inhibited growth by 50% following a 3-day exposure) value of 7 micrograms/ml. In actively growing cultures, the addition of quercetin resulted in the accumulation of cells at the G2-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 cell line. This inhibition takes place at the translational level. Quercetin did not affect the steady-state mRNA levels of p53, but prevented the accumulation of newly synthesized p53 protein. This quercetin action appeared to be somewhat specific for p53 because the drug did not alter the amount of other proteins present in MDA-MB468 cells such as P-glycoprotein and did not prevent the induction of the synthesis of epidermal growth factor receptor in response to epidermal growth factor.
Avila
M A
MA
Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20007.
Velasco
J A
JA
Cansado
J
J
Notario
V
V
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D009154:Mutation; D011794:Quercetin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D011794:Quercetin