Huang, Chi-ChangChi-ChangHuangLo, Chiu-PingChiu-PingLoChiu, Chih-YangChih-YangChiuShyur, Lie-FenLie-FenShyur2012-10-192018-07-062012-10-192018-07-062010http://ntur.lib.ntu.edu.tw//handle/246246/243203Background 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 g·mL -1) significantly inhibited colony formation, cell proliferation, migration and invasion of TS/A cells and induced G 2/M arrest and apoptosis in TS/A cells. c-Jun N-terminal kinase-mediated p21 Waf1/Cip1 expression and caspase activation cascades were up-regulated by DET, effects suppressed by N-acetyl-L-cysteine. Moreover, tumour necrosis factor -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. ? 2010 The British Pharmacological Society. All rights reserved.en-USChemoprevention; Deoxyelephantopin; Elephantopus scaber; Lung metastasis; Mammary adenocarcinoma[SDGs]SDG3acetylcysteine; antineoplastic agent; cyclin dependent kinase inhibitor 1; cyclooxygenase 2; deoxyelephantopin; gelatinase B; immunoglobulin enhancer binding protein; paclitaxel; reactive oxygen metabolite; sesquiterpene lactone derivative; stress activated protein kinase; tumor necrosis factor alpha; unclassified drug; vasculotropin; animal cell; animal experiment; animal model; apoptosis; article; breast adenocarcinoma; cancer inhibition; cancer survival; cell cycle arrest; cell invasion; cell migration; cell proliferation; colony formation; drug efficacy; drug mechanism; female; immunoblotting; immunohistochemistry; lung metastasis; mouse; nonhuman; priority journal; tumor model; Adenocarcinoma; Animals; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; Breast Neoplasms; Caspases; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Cyclooxygenase 2; Dose-Response Relationship, Drug; Female; Humans; JNK Mitogen-Activated Protein Kinases; Lactones; Lung Neoplasms; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Neoplasm Invasiveness; NF-kappa B; Paclitaxel; Reactive Oxygen Species; Sesquiterpenes; Time Factors; Tumor Burden; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assaysjournal article10.1111/j.1476-5381.2009.00581.xhttp://ntur.lib.ntu.edu.tw/bitstream/246246/243203/-1/137.pdf