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J Agric Food Chem. 2015 Aug 26;63(33):7317-25. doi: 10.1021/acs.jafc.5b03374. Epub 2015 Aug 13.

Sesamin Inhibits PDGF-Mediated Proliferation of Vascular Smooth Muscle Cells by Upregulating p21 and p27.

Author information

1
Department of Pharmacology, Chungnam National University College of Pharmacy , Daejeon 305-764, Republic of Korea.
2
KM Application Center, Korea Institute of Oriental Medicine , Daegu 701-300, Republic of Korea.
3
Department of Natural Product Chemistry, Chungnam National University College of Pharmacy , Daejeon 305-764, Republic of Korea.
4
Institute of Drug Research & Development, Chungnam National University , Daejeon 305-764, Republic of Korea.

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.

KEYWORDS:

cyclin-dependent kinase inhibitor; platelet-derived growth factor; proliferation; sesamin; vascular smooth muscle cell

PMID:
26244686
DOI:
10.1021/acs.jafc.5b03374
[Indexed for MEDLINE]

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