Quercetin regulates growth of Ishikawa cells through the suppression of EGF and cyclin D1.
Quercetin and other polyphenols have anti-carcinogenic and anti-tumorigenic activity in various organs, however, studies of this activity are lacking in endometrial cancer. We hypothesize that quercetin has anti-proliferative activity and the mechanisms of quercetin action may be through modulation of cell cycle and cell growth regulatory genes. To test this hypothesis, we treated endometrial cancer cells (Ishikawa cell line) with quercetin, and cell proliferation, expression of growth signal genes (EGF, VEGF, and TGF-alpha), cell cycle genes (p53, p21, p73, and cyclin D1), and apoptosis-related genes (bcl-2 and bax) were analyzed. Results of these experiments demonstrate that after a 7-day exposure to 1, 10 and 100 micro M of quercetin, growth of Ishikawa cells was inhibited by 3, 51 and 87%, respectively. The gene and protein expression data suggest that quercetin treatment (100 micro M) significantly decreased EGF and cyclin D1, whereas VEGF was up-regulated in Ishiwaka cell lines. Other genes such as TGF-alpha, p53, p21, p73, bcl-2 and bax were not significantly changed with quercetin treatment in Ishiwaka cell lines. The present study suggests that quercetin can suppress proliferation of Ishikawa cells through down-regulation of EGF and cyclin D1.
Kaneuchi
Masanori
M
Department of Urology, University of California, and Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Sasaki
Masahiro
M
Tanaka
Yuichiro
Y
Sakuragi
Noriaki
N
Fujimoto
Seiichiro
S
Dahiya
Rajvir
R
D019938:Cyclin D1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000235:genetics; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008222:Lymphokines / Q000235:genetics; D011794:Quercetin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019938:Cyclin D1; D004815:Epidermal Growth Factor; D011794:Quercetin