Curcumin is a potent broad spectrum inhibitor of matrix metalloproteinase gene expression in human astroglioma cells.
The abnormal expression of matrix metalloproteinases (MMPs) plays an important role in the invasion of malignant gliomas into the surrounding normal brain tissue. This study showed that curcumin has broad-spectrum inhibitory activity against MMP gene expression in human astroglioma cells. RNase protection assay showed that curcumin inhibited the PMA-induced mRNA expression of MMP-1, -3, -9, and -14. Curcumin repressed the DNA binding and transcriptional activities of AP-1, which is a common upstream modulator of MMP-1, -3, and -9 gene expression. In addition, curcumin suppressed the PMA-induced MAP kinase activities, which were differentially involved in modulating the MMPs. This suggests that the inhibition of MMP transcriptions by curcumin is mediated at least in part through the AP-1 and MAP kinase pathways. Curcumin was also found to significantly repress the in vitro invasion of glioma cells. Therefore, the broad-spectrum inhibition of MMP gene expression by curcumin might provide a novel therapeutic strategy for treating gliomas.
Kim
So-Young
SY
Department of Neuroscience, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Jung
Soo-Hyun
SH
Kim
Hee-Sun
HS
D000970:Antineoplastic Agents / Q000494:pharmacology; D001254:Astrocytoma / Q000201:enzymology*; D001483:Base Sequence; D001932:Brain Neoplasms / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases; D012260:Ribonucleases; D020782:Matrix Metalloproteinases; D003474:Curcumin