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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Breast Neoplasms / drug therapy
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Breast Neoplasms / enzymology
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Cell Line, Tumor
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Curcumin / pharmacology*
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Curcumin / therapeutic use
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Down-Regulation / drug effects
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Female
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Gene Expression Regulation, Neoplastic / drug effects*
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Humans
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Immediate-Early Proteins / biosynthesis*
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Male
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Melanoma / drug therapy
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Melanoma / enzymology*
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Mice
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Mice, Inbred C57BL
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Neoplasm Metastasis
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Neoplasms, Experimental
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Prostatic Neoplasms / drug therapy
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Prostatic Neoplasms / enzymology
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Protein Tyrosine Phosphatases / biosynthesis*
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Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors
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Reverse Transcriptase Polymerase Chain Reaction
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STAT3 Transcription Factor / antagonists & inhibitors
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Transcription, Genetic / drug effects
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Tumor Suppressor Protein p53 / drug effects
Substances
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Antineoplastic Agents
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Immediate-Early Proteins
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Ptp4a3 protein, mouse
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STAT3 Transcription Factor
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Tumor Suppressor Protein p53
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Proto-Oncogene Proteins pp60(c-src)
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Protein Tyrosine Phosphatases
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Curcumin