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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

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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.

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Abbreviations

C3G:

Cyanidin-3-glucoside

DHE:

Dihydroethidium

JAK/STAT:

Janus kinase/signal transducer and activator of transcription

NoxA1:

Nox activator 1

HBSS:

Hank’s balanced salt solution

PVDF:

Polyvinylidene fluoride

ROS:

Reactive oxygen Species

STAT3:

Signal transducer and activator of transcription 3

VSMCs:

Vascular smooth muscle cells

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Acknowledgments

This study was supported by grants from the Key Project of National Natural Science Foundation of China (30730079). All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Nutrition, School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, People’s Republic of China

    Xiaoqin Luo, Yunjun Xiao, Fenglin Song, Tangbin Zou, Min Wang, Min Xia & Wenhua Ling

  2. Department of Nutrition, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, People’s Republic of China

    Shi Fang

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  1. Xiaoqin Luo
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  7. Min Xia
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Correspondence to Wenhua Ling.

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S. Fang is the co-first author.

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Luo, X., Fang, S., Xiao, Y. et al. 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. Mol Cell Biochem 362, 211–218 (2012). https://doi.org/10.1007/s11010-011-1144-3

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  • DOI: https://doi.org/10.1007/s11010-011-1144-3

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