TY - JOUR T1 - An Anticancer Effect of Curcumin Mediated by Down-Regulating Phosphatase of Regenerating Liver-3 Expression on Highly Metastatic Melanoma Cells JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1238 LP - 1245 DO - 10.1124/mol.109.059105 VL - 76 IS - 6 AU - Lu Wang AU - Yan Shen AU - Ran Song AU - Yang Sun AU - Jianliang Xu AU - Qiang Xu Y1 - 2009/12/01 UR - http://molpharm.aspetjournals.org/content/76/6/1238.abstract N2 - 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.© 2009 The American Society for Pharmacology and Experimental Therapeutics ER -