Journal
BIOCHEMICAL PHARMACOLOGY
Volume 81, Issue 10, Pages 1192-1200Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2011.02.017
Keywords
AP-1; Cudratricusxanthone G (CTXG); Invasion; MMP-2; Rac1
Categories
Funding
- Research Platform of Cell Signaling Networks [06DZ22923]
- Shanghai Scientific Development Foundation from the Science and Technology Commission of Shanghai Municipality [074319104]
- Ministry of Science and Technology of the PR China [2009ZX09103-437]
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Cudratricusxanthone G (CTXG), a natural bioactive cudratricusxanthone extracted from C. tricuspidata, has shown anti-cancer properties. However, the function and mechanism of CTXG in tumor invasion have not been elucidated to date. In this study, we investigated the inhibitory effect of CTXG on the proliferation, migration and invasion of SW620 cells. We found that MMP-2, a pivotal factor in tumor invasion, was suppressed in both expression and activation by CTXG in a dose-dependent manner. The suppression of MMP-2 expression by CTXG led to an inhibition of SW620 cells invasion and migration by inactivating Rac1 and Cdc42 but not RhoA GTPase. Furthermore, CTXG also inhibited the transcriptional activity of AP-1 (activator protein-1). In conclusion, our data demonstrate that CTXG exerted antiinvasion action in SW620 cells by targeting MMP-2 though regulating the activities of Rac1, Cdc42 and their downstream transcriptional factor AP-1. These results are the first to reveal the novel functions of CTXG in cancer cell invasion and its molecular basis for the anti-cancer action. (C) 2011 Elsevier Inc. All rights reserved.
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