Genistein inhibits rat aortic smooth muscle cell proliferation through the induction of p27kip1.
Diet is one of the most important factors that influence the risks for cardiovascular diseases. Genistein, an isoflavone found in soy, may benefit the cardiovascular system. Here, we investigated the effect of genistein on platelet-derived growth factor (PDGF)-BB-induced proliferation of primary cultured rat aortic smooth muscle cells (RASMCs). Genistein significantly inhibited 25 ng/ml PDGF-BB-induced RASMC proliferation and [3H]-thymidine incorporation into DNA at 10, 20, and 40 microM. In accordance with these findings, genistein blocked the PDGF-BB-inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells. Western blot analysis showed that genistein not only inhibited phosphorylation of retinoblastoma protein (pRb) and expression of cyclin E, cyclin-dependent kinase (CDK) 2, and proliferating cell nuclear antigen (PCNA) protein, but also inhibited downregulation of cyclin-dependent kinase inhibitor (CKI) p27kip1. However, genistein did not affect p21cip1, CDK4, and cyclin D1 expression or early signal transduction through PDGF beta-receptor, extracellular signal-regulated kinases 1/2 (ERK1/2), Akt, and phospholipase C (PLC) gamma1 phosphorylation. These results suggest that genistein inhibits PDGF-BB-induced RASMC proliferation via G0/G1 arrest in association with induction of p27kip1, which may contribute to the beneficial effects of genistein on the cardiovascular system.
Yu
Ji-Yeon
JY
College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University, Korea.
Lee
Jung-Jin
JJ
Lim
Yong
Y
Kim
Tack-Joong
TJ
Jin
Yong-Ri
YR
Sheen
Yhun Y
YY
Yun
Yeo-Pyo
YP
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D000077214:Becaplermin; D015153:Blotting, Western; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
D002317:Cardiovascular Agents; C493962:Cdkn1b protein, rat; D016213:Cyclins; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D020574:Proto-Oncogene Proteins c-sis; D016160:Retinoblastoma Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000077214:Becaplermin; D019833:Genistein; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt; D018844:Cyclin-Dependent Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D051966:Phospholipase C gamma