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Research ArticleArticle

An Anticancer Effect of Curcumin Mediated by Down-Regulating Phosphatase of Regenerating Liver-3 Expression on Highly Metastatic Melanoma Cells

Lu Wang, Yan Shen, Ran Song, Yang Sun, Jianliang Xu and Qiang Xu
Molecular Pharmacology December 2009, 76 (6) 1238-1245; DOI: https://doi.org/10.1124/mol.109.059105
Lu Wang
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Yan Shen
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Ran Song
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Yang Sun
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Jianliang Xu
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Qiang Xu
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Abstract

Phosphatase of regenerating liver-3 (PRL-3) has been suggested as a potential target for anticancer drugs based on its involvement in tumor metastasis. However, little is known about a small-molecule inhibitor against PRL-3. In this study, we report that curcumin, the component of the spice turmeric, shows its antitumor effect by selectively down-regulating the expression of PRL-3 but not its family members PRL-1 and -2 in a p53-independent way. Curcumin inhibited the phosphorylation of Src and stat3 partly through PRL-3 down-regulation. Cells with PRL-3 stably knocked down show less sensitivity to curcumin treatment, which reveals that PRL-3 is the much further upstream target of curcumin. Curcumin treatment also remarkably prevented B16BL6 from invading the draining lymph nodes in the spontaneous metastatic tumor model, which is probably of relevance to PRL-3 down-regulation. Our results reveal a novel capacity of curcumin to down-regulate oncogene PRL-3, raising its possibility in therapeutic regimen against malignant tumor.

Footnotes

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

  • This study was supported in part by the Natural Science Foundation of China [Grant 30730107]; the Science Fund for Creative Research Groups [Grant 30821006]; and the Natural Science Foundation of Jiangsu Province [Grant BK2008022].

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

    doi:10.1124/mol.109.059105

  • ABBREVIATIONS:

    PRL
    phosphatase of regenerating liver
    DMEM
    Dulbecco's modified Eagle's medium
    DMSO
    dimethyl sulfoxide
    FBS
    fetal bovine serum
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    PBS
    phosphate-buffered saline
    PCR
    polymerase chain reaction
    siRNA
    small interfering RNA
    RT-PCR
    reverse transcription-polymerase chain reaction
    bp
    base pair.

    • Received July 3, 2009.
    • Accepted September 24, 2009.
  • © 2009 The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 76 (6)
Molecular Pharmacology
Vol. 76, Issue 6
1 Dec 2009
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Research ArticleArticle

An Anticancer Effect of Curcumin Mediated by Down-Regulating Phosphatase of Regenerating Liver-3 Expression on Highly Metastatic Melanoma Cells

Lu Wang, Yan Shen, Ran Song, Yang Sun, Jianliang Xu and Qiang Xu
Molecular Pharmacology December 1, 2009, 76 (6) 1238-1245; DOI: https://doi.org/10.1124/mol.109.059105

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Research ArticleArticle

An Anticancer Effect of Curcumin Mediated by Down-Regulating Phosphatase of Regenerating Liver-3 Expression on Highly Metastatic Melanoma Cells

Lu Wang, Yan Shen, Ran Song, Yang Sun, Jianliang Xu and Qiang Xu
Molecular Pharmacology December 1, 2009, 76 (6) 1238-1245; DOI: https://doi.org/10.1124/mol.109.059105
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