Quercetin enhances transforming growth factor β₁, secretion by human ovarian cancer cells

Abstract

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 125I-TGF beta 1 from binding to its receptor; moreover Q (10 microM) 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 a 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 microM) exposure revealed that there was no increase, suggesting that regulation of TGF beta 1 occurs at posttranscriptional levels.

In vitro Antioxidant and Antiproliferative Activities of Flavonoids from Ailanthus excelsa (Roxb.) (Simaroubaceae) Leaves

“…Both, quercetin 3-O-β-galactoside (10) and quercetin 3-O-α-arabinoside (9) are able to inhibit lung large cell carcinoma proliferation with IC 50 values of 3.2 and 7.5 μg ml -1 , respectively. Several studies have been done on fl avonoids' antiproliferative effects against human ovarian, leukemic, intestinal, lung, breast and bladder cancer cells (Scambia et al, 1994;Agullo et al, 1997;Narayanan et al, 1999;Uddin and Choudhry, 1995).…”

The Flavonoid Quercetin Regulates Growth and Gene Expression in Rat FRTL-5 Thyroid Cells

“…It has been reported that in some type of cancer cells, the antiproliferative effect of quercetin is mediated by TGF-␤1. Thus, quercetin induces a release of TGF-␤1 that acts in an autocrine manner inhibiting cell growth (39,40). Because TGF-␤1 inhibits growth in several thyroid culture cells including FRTL-5 through phosphorylation of Smad proteins (41-43), we investigated whether this was the mechanism involved in the quercetin antiproliferative effect.…”

“…It has been reported that one of the mechanisms by which quercetin suppress growth in cancer cells is through an increase of TGF-␤1 activity (39,40). This increase is time de- pendent (starting after 4 h of treatment and reaching a maximum after 24 h) and occurs at a posttranscriptional level.…”

Quercetin Is Able to Demethylate the p16INK4a Gene Promoter

“…Quercetin is the most widely distributed flavonoid, found in apples, onions, black tea and red wine [9] . Studies in vitro and in vivo have suggested that quercetin may have a protective role against colon [10][11][12] , breast [13] and ovarian [14] cancers.…”