title: Cyanidin-3-glucoside suppresses TNF-α-induced cell proliferation through the repression of Nox activator 1 in mouse vascular smooth muscle cells: involvement of the STAT3 signaling.
abstract: Cyanidin-3-glucoside (C3G) is a member of the anthocyanin family which belongs to the flavonoid class and possesses antiatherogenic properties. Many studies have demonstrated the protective effects of C3G on vascular endothelial cells and monocytes, however, the precise effects on vascular smooth muscle cells (VSMCs) have been less thoroughly studied. Hence, we investigated the role of C3G in TNF-α-induced VSMCs proliferation and explored the possible mechanisms. TNF-α stimulated VSMCs proliferation, and pretreatment with C3G inhibited the proliferation in dose- and time-dependent manners. Then, we found that C3G attenuated TNF-α-induced ROS over generation by Dihydroethidium staining. The combination of 50 μM C3G and 100 μM apocynin significantly reduced ROS generation. Moreover, C3G pretreatment significantly suppressed the expression of Nox activator 1, a subunit of NADPH oxidase in mouse VSMCs. C3G also inhibited TNF-α-induced signal transducer and activator of transcription (STAT3) phosphorylation, and the inhibitory effect was more prominent in C3G and apocynin co-pretreated cells than that pretreated with C3G or apocynin alone. Administration of the ROS scavenger catalase (2,000 U/ml) remarkably inhibited TNF-α-induced cell proliferation and STAT3 activation. These data suggest that C3G exerts its antiproliferative effect on TNF-α-induced VSMCs proliferation through inhibiting STAT3 activation by attenuating NoxA1-derived ROS over production.
authors: Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Xiaoqin
authors: X
authors: Luo
authors: Shi
authors: S
authors: Fang
authors: Yunjun
authors: Y
authors: Xiao
authors: Fenglin
authors: F
authors: Song
authors: Tangbin
authors: T
authors: Zou
authors: Min
authors: M
authors: Wang
authors: Min
authors: M
authors: Xia
authors: Wenhua
authors: W
authors: Ling
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005960:Glucosides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D048868:Adaptor Proteins, Signal Transducing; D000872:Anthocyanins; D005960:Glucosides; C472286:Noxa1 protein, mouse; D011506:Proteins; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C462279:cyanidin-3-O-beta-glucopyranoside; C056165:acetovanillone; D002374:Catalase