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

Our study demonstrates that quercetin (Q)-induced growth-inhibitory ac tivity in ovarian cancer cells may be mediated by modulation of transf orming growth factor beta(1) (TGF beta(1)) production. We used the OVC A 433 cell line which is very sensitive to the anti-proliferative effe ct of Q and expresses high-affinity, low-capacity TGF beta(1) receptor s. 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) inc reases 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 b oth in OVCA 433 and in clonogenic assay of cells from a primary ovaria n 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) sec retion. Northern-blot analysis of TGF beta(1) mRNA levels at various t imes of Q (10 mu M) exposure revealed that there was no increase, sugg esting that regulation of TGF beta(1) occurs at posttranscriptional le vels. (C) 1994 Wiley-Liss, Inc.