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Abstract
Matrix metalloproteinases (MMPs) play an active role in facilitating the invasion of cancer cells with excessive extracellular matrix (ECM) degradation. In the present study, we investigated the antiinvasive effects of isorhamnetin, a naturally occurring flavonoid, on MDA-MB-231 human breast carcinoma cells. The results indicated that isorhamnetin significantly inhibited the adhesion, migration, and invasion of the cells in vitro. Moreover, isorhamnetin suppressed the activity and expression of MMP-2 and MMP-9, which were determined by gelatin zymography, real-time PCR, and Western blot analysis, respectively. Besides, isorhamnetin had little effect on the secretion of urokinase plasminogen activator. Further elucidation of the mechanism revealed that isorhamnetin exerted an inhibitory effect on the phosphorylation of p38 and STAT3, although it had no effect on ERK1/2 and JNK. Taken together, these data demonstrated that isorhamnetin could significantly inhibit the invasion of MDA-MB-231 cells by downregulating the expression and activity of MMP-2 and MMP-9, which was potentially associated with the suppression of p38 MAPK and STAT3. Therefore, the findings provide new evidence for the anti-cancer activity of isorhamnetin.
ACKNOWLEDGMENT
Chenglin Li and Dan Yang contributed equally to this work.
FUNDING
This work was supported by the Natural Science Foundation of China (No. 21205102, 81402969, and 81402789), the Natural Science Foundation of Jiangsu province (No. BK20130220), the China Postdoctoral Science Foundation funded project (2013M541733), the Jiangsu Planned Projects for Postdoctoral Research Funds (1301015B), the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (13KJB350007), and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
SUPPLEMENTAL DATA
Supplemental data for this article can be accessed on the publisher's website.
