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
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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
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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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