Curcumin suppresses phorbol ester-induced matrix metalloproteinase-9 expression by inhibiting the PKC to MAPK signaling pathways in human astroglioma cells.
The aberrant expression of matrix metalloproteinase-9 (MMP-9) is implicated in the invasion and angiogenesis process of brain tumor. This study has investigated the effects of curcumin on MMP-9 expression in human astroglioma cell lines. Curcumin significantly inhibited the MMP-9 enzymatic activity and protein expression that was induced by PMA. The inhibitory effect of curcumin on MMP-9 expression correlates with the decreased MMP-9 mRNA level and the suppression of MMP-9 promoter activity. The curcumin-mediated inhibition of MMP-9 gene expression appears to occur via NF-kappaB and AP-1 because their DNA binding activities were suppressed by curcumin. Furthermore, curcumin strongly repressed the PMA-induced phosphorylation of ERK, JNK, and p38 MAP kinase, which were dependent on the PKC pathway. Therefore, the inhibition of MMP-9 expression by curcumin might have therapeutic potential for controlling the growth and invasiveness of brain tumor.
Woo
Moon-Sook
MS
Department of Neuroscience, Ewha Institute of Neuroscience, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Jung
Soo-Hyun
SH
Kim
So-Young
SY
Hyun
Jin-Won
JW
Ko
Kwang-Ho
KH
Kim
Won-Ki
WK
Kim
Hee-Sun
HS
D000970:Antineoplastic Agents / Q000008:administration & dosage; D001254:Astrocytoma / Q000201:enzymology*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage*; D004347:Drug Interactions; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010703:Phorbol Esters / Q000008:administration & dosage*; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D010703:Phorbol Esters; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D003474:Curcumin