Crocetin suppresses angiotensin II-induced vascular smooth-muscle cell proliferation through inhibition of ERK1/2 activation and cell-cycle progression.
Excessive proliferation of vascular smooth cells (VSMCs) plays a critical role in the development of atherosclerosis, and inhibition of VSMCs proliferation has been proved to be beneficial to this disease. In the present study, we investigated the antiproliferative effect of crocetin, a carotinoid (Fig. 1, >98%, HPLC) with potent antioxidant capacity, on bovine aortic VSMCs (BASMCs), and the possible mechanisms involved. The results indicate that crocetin potently inhibited AngII-induced BASMC proliferation, as evaluated by MTT assay and [3H]-thymidine incorporation assay. Flow cytometry analysis showed that crocetin markedly blocked AngII-induced cell-cycle progression by arresting the cells in the G0/G1 phase. Consistently, crocetin markedly suppressed AngII-induced activation of extracellular signal-regulated kinase1/2 (ERK1/2) and its downstream effector c-fos expression, which is a prerequisite for cell-cycle progression. In addition, crocetin significantly decreased AngII-induced intracellular reactive oxygen species and increased the activity of superoxide dismutase. Taken together, these results indicate that crocetin was capable of inhibiting BASMC proliferation by blocking cell-cycle progression, which might be associated with the suppression of ERK1/2 activation and c-fos expression. These results might be related, at least partly, to the antioxidant property of crocetin.
Zheng
Shuguo
S
Department of Pharmacology, Wannan Medical College, Wuhu, China. zhengsg2000@163.com
Qian
Zhiyu
Z
Wen
Na
N
Xi
Liang
L
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002338:Carotenoids / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015394:Molecular Structure; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives
D000975:Antioxidants; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C487773:trans-sodium crocetinate; D014801:Vitamin A; D000804:Angiotensin II; D002338:Carotenoids; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases