title: Sesamin Inhibits PDGF-Mediated Proliferation of Vascular Smooth Muscle Cells by Upregulating p21 and p27.
abstract: Sesamin, an active ingredient of Asiasarum heterotropoides, is known to exhibit many bioactive functions, but the effect thereof on vascular smooth muscle cell (VSMC) proliferation remains poorly understood. Hence, we explored the antiproliferative action of sesamin on VSMCs and the underlying mechanism thereof, focusing on possible effects of sesamin on cell cycle progression. Sesamin significantly inhibited platelet-derived growth factor (PDGF)-induced VSMC proliferation (inhibition percentage at 1, 5, and 10 μM sesamin was 49.8 ± 22.0%, 74.6 ± 19.9%, and 87.8 ± 13.0%, respectively) in the absence of cytotoxicity and apoptosis, and PDGF-induced DNA synthesis; and arrested cell cycle progression in the G0/G1-to-S phase. Sesamin potently inhibited cyclin D1 and CDK4 expression, pRb phosphorylation, and expression of the proliferating cell nuclear antigen (PCNA); and upregulated p27(KIP1), p21(CIP1), and p53. The results thus indicate that the antiproliferative effect of sesamin on PDGF-stimulated VSMCs is attributable to arrest of the cell cycle in G0/G1 caused, in turn, by upregulation of p27(KIP1), p21(CIP1), and p53, and inhibition of cyclin E-CDK2 and cyclin D1-CDK4 expression.
authors.affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy , Daejeon 305-764, Republic of Korea.
authors.forename: Joo-Hui
authors.initials: JH
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy , Daejeon 305-764, Republic of Korea.
authors.forename: Sang-Gil
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy , Daejeon 305-764, Republic of Korea.
authors.forename: Sang-Hyuk
authors.initials: SH
authors.lastname: Jung
authors.affiliation: KM Application Center, Korea Institute of Oriental Medicine , Daegu 701-300, Republic of Korea.
authors.forename: Jung-Jin
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy , Daejeon 305-764, Republic of Korea.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Natural Product Chemistry, Chungnam National University College of Pharmacy , Daejeon 305-764, Republic of Korea.|Institute of Drug Research & Development, Chungnam National University , Daejeon 305-764, Republic of Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy , Daejeon 305-764, Republic of Korea.|Institute of Drug Research & Development, Chungnam National University , Daejeon 305-764, Republic of Korea.
authors.forename: Chang-Seon
authors.initials: CS
authors.lastname: Myung
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D004149:Dioxoles / Q000494:pharmacology*; D017705:Lignans / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D034741:RNA, Small Interfering; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C493958:Cdkn1a protein, rat; C493962:Cdkn1b protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004149:Dioxoles; D017705:Lignans; D010982:Platelet-Derived Growth Factor; D034741:RNA, Small Interfering; D050760:Cyclin-Dependent Kinase Inhibitor p27; C054125:sesamin
keywords: cyclin-dependent kinase inhibitor; platelet-derived growth factor; proliferation; sesamin; vascular smooth muscle cell