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 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.
Scambia
G
G
Department of Gynecology, Catholic University, Rome, Italy.
Panici
P B
PB
Ranelletti
F O
FO
Ferrandina
G
G
De Vincenzo
R
R
Piantelli
M
M
Masciullo
V
V
Bonanno
G
G
Isola
G
G
Mancuso
S
S
D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016212:Transforming Growth Factor beta; D011794:Quercetin