Luteolin prevents PDGF-BB-induced proliferation of vascular smooth muscle cells by inhibition of PDGF beta-receptor phosphorylation.
Luteolin occurs as glycosylated forms in celery, green pepper, perilla leaf and camomile tea, and has been shown to possess antimutagenic, antitumorigenic, antioxidant and antiinflammatory properties. In this study, we have investigated the antiproliferable effect and its mechanism of luteolin on platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic vascular smooth muscle cells (VSMCs). Luteolin significantly inhibited PDGF-BB-induced proliferation and DNA synthesis of rat aortic VSMCs in a concentration-dependent manner. In addition, flow cytometry analysis of DNA content revealed blocking of the PDGF-BB-inducible cell cycle progression by luteolin. Pre-incubation of rat aortic VSMCs with luteolin significantly inhibited the PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and phospholipase C (PLC)-gamma1 activation as well as c-fos gene expression. Consisted with these findings, luteolin inhibited PDGF-Rbeta phosphorylation induced by PDGF-BB in a concentration-dependent manner. These results suggest that the inhibitory effect of luteolin on the PDGF-BB-induced proliferation of rat aortic VSMCs may be mediated by blocking phosphorylation of PDGF-Rbeta.
Kim
Jin-Ho
JH
College of Pharmacy, Chungbuk National University, 48 Gaeshin-Dong, Heungduk-Gu, Cheongju 361-763, South Korea.
Jin
Yong-Ri
YR
Park
Beoung-Soo
BS
Kim
Tack-Joong
TJ
Kim
Soo-Yeon
SY
Lim
Yong
Y
Hong
Jin-Tae
JT
Yoo
Hwan-Soo
HS
Yun
Yeo-Pyo
YP
D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000494:pharmacology*; D047311:Luteolin / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D006131:Growth Inhibitors; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D047311:Luteolin