Abstract
Phosphatase of regenerating live-3 (PRL-3) has been suggested as a potential target for anti-cancer drugs based on its involvement in tumor metastasis. However, little is known about small molecule inhibitor against PRL-3. In this study, we report that curcumin, the component of the spice turmeric, shows its anti-tumor 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 of curcumin treatment, which reveals that PRL-3 is the very upstream target of curcumin. Curcumin treatment also remarkably prevented B16BL6 from invading the draining lymph nodes in the spontaneous metastatic tumor model, which is likely 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.
- Protein tyr Phosphatases
- Regulation of gene expression
- Regulation - transcriptional
- Transcription targets
Footnotes
- Received July 3, 2009.
- Revision received September 23, 2009.
- Accepted September 24, 2009.
- The American Society for Pharmacology and Experimental Therapeutics