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

Background and purpose: Elephantopus scaber L. (Asteraceae) is a traditional herbal medicine with anti‐cancer effects. We evaluated the in vitro and in vivo efficacy of a major sesquiterpene lactone constituent of E. scaber, deoxyelephantopin (DET), against mammary adenocarcinoma and the underlying molecular mechanism. Experimental approach: A variety of cellular assays, immunoblotting and immunohistochemistry, as well as both orthotopic and metastatic TS/A tumour models in BALB/c mice, were used. Test mice were pretreated and post‐treated with DET or paclitaxel and mammary tumour growth evaluated. Key results: DET (≤2 µg·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. c‐Jun N‐terminal kinase‐mediated p21Waf1/Cip1 expression and caspase activation cascades were up‐regulated by DET, effects suppressed by N‐acetyl‐L‐cysteine. Moreover, tumour necrosis factor α‐induced matrix metalloproteinase‐9 enzyme activity and expression and nuclear factor‐kappa B activation were abolished by DET. Pretreatment with DET was more effective than paclitaxel, for profound suppression of orthotopic tumour growth (99% vs. 68% reduction in tumour 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 cyclooxygenase‐2 and vascular endothelial growth factor in metastatic lung tissues of TS/A‐bearing mice were attenuated by DET. Conclusions and implications: Our data provide evidence for the suppression of mammary adenocarcinoma by DET with several mechanisms and suggest that DET has potential as a chemopreventive agent for breast cancer.