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.
ASJC Scopus subject areas
- Drug Discovery
- Clinical Biochemistry
- Molecular Medicine
Chao, R., Chow, J. M., Hsieh, Y. H., Chen, C. K., Lee, W. J., Hsieh, F. K., Yu, N. Y., Chou, M. C., Cheng, C. W., Yang, S. F., & Chien, M. H. (2015). 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. Expert Opinion on Therapeutic Targets, 19(10), 1293-1306. https://doi.org/10.1517/14728222.2015.1075509