QUERCETIN ENHANCES TRANSFORMING GROWTH-FACTOR BETA(1) SECRETION BY HUMAN OVARIAN-CANCER CELLS

Our study demonstrates that quercetin (Q)-induced growth-inhibitory activity in ovarian cancer cells may be mediated by modulation of transforming growth factor beta(1) (TGF beta(1)) production. We used the OVCA 433 cell line which is very sensitive to the anti-proliferative effect of Q and expresses high-affinity, low-capacity TGF beta(1) receptors. Conditioned medium (CM) from Q-treated cells is able to displace I-125-TGF beta(1) from binding to its receptor; moreover Q (10 mu M) increases TGF beta(1) activity in CM in a time-dependent fashion starting after 4 hr and reaching a maximum by 24 hr of Q treatment. Q-induced growth inhibition is reversed by a neutralizing anti-TGF beta(1) MAb both in OVCA 433 and in clonogenic assay of cells from a primary ovarian tumor. Q-induced increase of TGF beta(1) activity in CM is specific since other anti-proliferative compounds, such as Dexamethasone, which is as active on the cell cycle as Q, had no effect on TGF beta(1) secretion. Northern-blot analysis of TGF beta(1) mRNA levels at various times of Q (10 mu M) exposure revealed that there was no increase, suggesting that regulation of TGF beta(1) occurs at posttranscriptional levels. (C) 1994 Wiley-Liss, Inc.