Inhibition of matrix metalloproteinase-9 gene expression by an isoflavone metabolite, irisolidone in U87MG human astroglioma cells.
Matrix metalloproteinase-9 (MMP-9) plays an important role in mediating the invasion and angiogenic process of malignant gliomas. This study was undertaken to determine if an isoflavone metabolite, irisolidone, inhibits MMP-9 expression in human astroglioma cells. Irisolidone was found to inhibit the secretion and protein expression of MMP-9 induced by PMA in U87 MG glioma cells, accompanied by the inhibition of MMP-9 mRNA expression and promoter activity. Further mechanistic studies revealed that irisolidone inhibits the binding of NF-kappaB and AP-1 to the MMP-9 promoter and suppresses the PMA-induced phosphorylation of ERK and JNK, which are upstream signaling molecules in MMP-9 expression. The Matrigel-invasion assay showed that irisolidone suppresses the in vitro invasiveness of glioma cells. Therefore, the strong inhibition of MMP-9 expression by irisolidone might be a potential therapeutic modality for controlling the growth and invasiveness of gliomas.
Kim
So-Young
SY
Department of Neuroscience and Medical Research Institute, College of Medicine, Ewha Womans University, Mok-6-dong 911-1, Yangchun-Ku, Seoul 158-710, Republic of Korea.
Lee
Eun-Jung
EJ
Woo
Moon-Sook
MS
Jung
Ji-Sun
JS
Hyun
Jin-Won
JW
Min
Sung-Won
SW
Kim
Dong-Hyun
DH
Kim
Hee-Sun
HS
D001254:Astrocytoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D005419:Flavonoids; D007529:Isoflavones; D016328:NF-kappa B; D018808:Transcription Factor AP-1; C423902:irisolidone; C065753:isoflavanone; D020780:Matrix Metalloproteinase 9