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Abstract Title:

Tricetin suppresses the migration/invasion of human glioblastoma multiforme cells by inhibiting matrix metalloproteinase-2 through modulation of the expression and transcriptional activity of specificity protein 1.

Abstract Source:

Expert Opin Ther Targets. 2015 ;19(10):1293-306. Epub 2015 Aug 6. PMID: 26245494

Abstract Author(s):

Rockey Chao, Jyh-Ming Chow, Yi-Hsien Hsieh, Chi-Kuan Chen, Wei-Jiunn Lee, Feng-Koo Hsieh, Nuo-Yi Yu, Ming-Chih Chou, Chao-Wen Cheng, Shun-Fa Yang, Ming-Hsien Chien

Article Affiliation:

Rockey Chao

Abstract:

OBJECTIVE: Glioblastoma multiforme (GBM) is a severely invasive tumor that can be fatal because it is difficult to treat. Tricetin, a natural flavonoid, was demonstrated to inhibit the growth of various cancers, but the effect of tricetin on cancer motility is largely unknown.

RESEARCH DESIGN AND METHODS: In the present study, we examined the anti-invasive properties of tricetin in huwman GBM cells.

RESULTS: Our results showed that tricetin inhibited the migration/invasion of two GBM cell lines. We found that tricetin inhibited MMP-2 expression in the GBM cells. Real-time polymerase chain reaction and promoter activity assays indicated that tricetin inhibited MMP-2 expression at the transcriptional level. Such inhibitory effects were associated with the suppression of specificity protein-1 (SP-1) DNA-binding activity. An examination of clinical samples revealed a positive correlation between SP-1 and MMP-2 in glioma specimens, and higher expression levels were correlated with a worse probability of survival. Moreover, blocking the extracellular signal-regulated kinase (ERK) pathway also inhibited MMP-2-mediated cell motility, and further enhanced the anti-invasive ability of tricetin in GBM cells.

CONCLUSIONS: SP-1 is an important target of tricetin for suppressing MMP-2-mediated cell motility in GBM cells, and a combination of tricetin and an ERK inhibitor may be a good strategy for preventing GBM invasion.

Study Type : In Vitro Study

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