Deoxyelephantopin, a novel multifunctional agent, suppresses mammary tumor growth and lung metastasis and doubles survival time in mice

Elephantopus scaber L. (Asteraceae) is a traditional herbal medicine known for its anti-cancer effect. We addressed the in vitro and in vivo bioefficacy of an abundant sesquiterpene lactone deoxyelephantopin (DET) isolated from E. scaber against mammary adenocarcinoma and the underlying molecular mechanism. Various in vitro cell-biological assays, immunoblotting and immunohistochemistry, as well as both orthotopic and metastatic TS/A tumor models in BALB/c mice, were used. Test mice were pre- and post-treated with DET or paclitaxel and evaluated for the effect on mammary tumor. DET ( 2 gmL-1) significantly inhibited colony formation, cell proliferation, migration and invasion of TS/A cells and induced G2/M arrest and apoptosis in TS/A cells. JNKmediated p21Waf1/Cip1 expression and caspase activation cascades were up-regulated by DET, which was significantly suppressed by N-acetyl-L-cysteine. Moreover, TNF-induced MMP-9 enzyme activity and expression and NF-B activation were abolished by DET. Pretreatment with DET was superior to that with paclitaxel, for profound suppression of orthotopic tumor growth (99% vs. 68% reduction in tumor size) and lung metastasis of TS/A cells (82% vs. 63% reduction in metastatic pulmonary foci) and prolonged median survival time (56 vs. 37 days, P < 0.01) in mice. The levels of COX-2 and VEGF in metastatic lung tissues of TS/A-bearing mice were attenuated by DET. This article provides science-based evidence for the novel function of DET in suppressing mammary adenocarcinoma by multiple mechanisms, which suggests that DET has great potential as a chemopreventive agent for breast cancer.

 

同研究人員:Chi-Chang Huang, Chiu-Ping Lo, Chih-Yang Chiu and Lie-Fen Shyur*