Polyphenol-rich extract from mulberry leaf inhibits vascular smooth muscle cell proliferation involving upregulation of p53 and inhibition of cyclin-dependent kinase.
This study was carried out to investigate the impact of polyphenol-rich extract from mulberry leaf on the proliferation of vascular smooth muscle cell (VSMC) and verify its mechanism in vitro. VSMC proliferation is an important pathophysiological process in the development of atherosclerosis, which is the major cause of coronary artery disease (CAD). Polyphenol-rich foods, such as mulberry leaf, have been reported to reduce the risk of CAD. The effect of mulberry leaf extract (MLE) on cell growth was measured by a growth curve assay, on distribution of cells in the cell cycle by flow cytometry, and on cyclin-dependent kinase (CDK) activity and cell-cycle regulatory proteins by Western blot, immunoblotting, and immunoprecipitation analyses. The results showed that MLE induced phosphorylation of p53, promoted expression of p21 and p27, decreased CDK2/4 activity, inhibited phosphorylation of Rb, and thereby blocked the G1 to S transition in the cell cycle.
Chan
Kuei-Chuan
KC
Department of Internal Medicine, Chung Shan Medical University Hospital, School of Medicine.
Ho
Hsieh-Hsun
HH
Peng
Chiung-Huei
CH
Lan
Kuang-Ping
KP
Lin
Ming-Cheng
MC
Chen
Hsiang-Mei
HM
Wang
Chau-Jong
CJ
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D050197:Atherosclerosis / Q000517:prevention & control; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003324:Coronary Artery Disease / Q000517:prevention & control; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D031625:Morus; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves / Q000737:chemistry*; D059808:Polyphenols; D051381:Rats; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D015854:Up-Regulation
D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D016159:Tumor Suppressor Protein p53; D018844:Cyclin-Dependent Kinases