title: Diethylstilbestrol induces arrest of rat vascular smooth muscle cell cycle progression through downregulation of cyclin D1 and cyclin E.
abstract: Cardiovascular disease is associated with a multitude of pathophysiologic conditions, including vascular smooth muscle cell (VSMC) proliferation in response to vessel injury. Diethylstilbestrol (DES) was previously prescribed for at-risk pregnancies to prevent abortion, miscarriage, and premature labor. Our aim in this study was to elucidate the effects and molecular mechanism of DES on proliferation and cell cycle progression of platelet-derived growth factor (PDGF)-BB-stimulated rat aortic VSMCs. Treating the cells with DES (1-7 μM) dramatically inhibited cell proliferation in a dose-dependent manner without any cytotoxic effects. In addition, DES blocked cell cycle progression from PDGF-BB-stimulated cells, which we found was related to down-regulation of the cell cycle regulatory factors, cyclin D1, and cyclin E. Our data demonstrate that DES inhibits rat aortic VSMC proliferation and cell cycle progression through regulation of cell cycle-related proteins. Therefore, our observations may explain, in part, the mechanistic basis underlying the therapeutic effects of DES in cardiovascular disease.
authors: Division of Biological Science and Technology, College of Science and Technology, Yonsei University, Wonju, Korea.
authors: Min-Cheol
authors: MC
authors: Song
authors: Junsoo
authors: J
authors: Park
authors: Tack-Joong
authors: TJ
authors: Kim
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D000077214:Becaplermin; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D056741:Cyclin D / Q000235:genetics / Q000378:metabolism*; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000494:pharmacology*; D015536:Down-Regulation; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D020935:MAP Kinase Signaling System; D008934:Mitogens / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D051381:Rats
chemical_list: D018797:Cell Cycle Proteins; D056741:Cyclin D; D019927:Cyclin E; D008934:Mitogens; D016760:Proto-Oncogene Proteins c-fos; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D004054:Diethylstilbestrol