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Research ArticleCellular and Molecular

Caffeic Acid 3,4-Dihydroxy-Phenethyl Ester Induces Cancer Cell Senescence by Suppressing Twist Expression

Anliang Dong, Yuanzhang Fang, Li Zhang, Juan Xie, Xian Wu, Lipeng Zhang, Xiaoyuan Lian, Yihua Chen, Jian Luo and Mingyao Liu
Journal of Pharmacology and Experimental Therapeutics October 2011, 339 (1) 238-247; DOI: https://doi.org/10.1124/jpet.111.181081
Anliang Dong
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Yuanzhang Fang
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Li Zhang
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Juan Xie
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Xian Wu
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Lipeng Zhang
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Xiaoyuan Lian
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Yihua Chen
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Jian Luo
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Mingyao Liu
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Abstract

Compared with traditional cytotoxic cancer therapy, therapy-induced cancer cell senescence attracts much interest because it is similarly effective, has fewer side effects, and is more efficiently cleared by immune cells. In this study, we demonstrate that unlike caffeic acid phenethyl ester, caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE), which is isolated from the medicinal plants Sarcandra glabra and Teucrium pilosum, inhibits human cancer cell growth and colony formation by inducing cancer cell senescence, not apoptosis. CADPE induces cell senescence and morphology changes by increasing cellular size and cytoplasmic granularity, enhancing senescence-associated β-galactosidase activity and differentiated embryo-chondrocyte expressed gene 1 expression, and blocking cell-cycle arrest in the G1 phase. To help understand the underlying mechanisms, we show that CADPE significantly suppressed the expression of Twist1 and led to the up-regulation of rat sarcoma, p53, p21WAF1/CIP1, and p16INK4a proteins in a dose-dependent manner, resulting in the hypophosphorylation of retinoblastoma protein. Furthermore, overexpression of Twist1 prevented CADPE-induced cell senescence in tumor cells. Therefore, our studies provide evidence for a novel role of CADPE in cancer cell senescence by targeting the Twist1-dependent senescence signaling pathway.

Footnotes

  • This work was supported by the Science and Technology Commission of Shanghai Municipality [Pujiang Program Grant 09PJ1403900]; the National Natural Science Foundation of China [Grants 30800653, 81071437, 30800627]; and the Fundamental Research Funds for the Central Universities and 973 Program [Grant 2010 CB529704].

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.111.181081.

  • ↵Embedded Image The online version of this article (available at http://jpet.aspetjournals.org) contains supplemental material.

  • ABBREVIATIONS:

    SA-β-gal
    senescence-associated β-galactosidase
    CAPE
    caffeic acid phenethyl ester
    CADPE
    caffeic acid 3,4-dihydroxyphenethyl ester
    DEC1
    differentiated embryo-chondrocyte expressed gene 1
    Ras
    rat sarcoma
    pRB
    retinoblastoma tumor suppressor
    SRB
    sulforhodamine B
    TCA
    trichloroacetic acid
    PI
    propidium iodide
    PARP
    poly(ADP)-ribose polymerase
    PCR
    polymerase chain reaction
    EGFP
    enhanced green fluorescence protein
    DMEM
    Dulbecco's modified Eagle's medium
    HUVEC
    human umbilical vascular endothelial cell
    NF-κB
    nuclear factor κB
    FACS
    fluorescence-activated cell sorting
    WT
    wild type
    STAT3
    signal transducer and activator of transcription 3 .

  • Received March 2, 2011.
  • Accepted July 11, 2011.
  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 339 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 339, Issue 1
1 Oct 2011
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Research ArticleCellular and Molecular

CADPE Induces Cancer Cell Senescence

Anliang Dong, Yuanzhang Fang, Li Zhang, Juan Xie, Xian Wu, Lipeng Zhang, Xiaoyuan Lian, Yihua Chen, Jian Luo and Mingyao Liu
Journal of Pharmacology and Experimental Therapeutics October 1, 2011, 339 (1) 238-247; DOI: https://doi.org/10.1124/jpet.111.181081

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Research ArticleCellular and Molecular

CADPE Induces Cancer Cell Senescence

Anliang Dong, Yuanzhang Fang, Li Zhang, Juan Xie, Xian Wu, Lipeng Zhang, Xiaoyuan Lian, Yihua Chen, Jian Luo and Mingyao Liu
Journal of Pharmacology and Experimental Therapeutics October 1, 2011, 339 (1) 238-247; DOI: https://doi.org/10.1124/jpet.111.181081
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