Deoxyelephantopin exhibits potent effects against breast tumor growth and metastasis in vitro and in vivo

Elephantopus scaber L. (Compositae) is a popularly used herbal tea constituent or folk medicine for various medications such as antitumor, anti-inflammation, etc. In this study, a group of sesquiterpene lactones (SLs) were isolated from the E. scaber extracts using silica gel chromatography and structurally elucidated by various spectral analyses. A most abundant SL compound, namely deoxyelephantopin (DET), was further examined for its anti-tumor cell activity in vitro and in vivo . We observed that DET exhibited a strong anti-breast cancer cell proliferation effect, with IC 50 value=1.5–2.0µg/ml, on either human (MCF-7) or murine (TS/A) cell line. DET also significantly induced cell-cycle arrest, apoptosis, and suppressed colony formation and cell migration in TS/A cells. We further investigated the preventive and therapeutic effects of DET on tumor growth and lung metastasis in vivo using TS/A tumor-bearing syngeneic BALB/c mouse model. We observed that DET exhibited profound effects on TS/A tumor formation. The TS/A tumor growth and size were found to be significantly suppressed in the DET-treated mice (10mg/kgBW) with a T/C value of 64% that was superior or comparable to the effect of Taxol®, a well-known therapeutic drug for breast cancer. In the lung metastasis model, vehicle-treated animals had a survival rate of 50% and 0% at 25 and 34 days, respectively, whereas DET pretreated animals not only significantly prolonged the overall survival rate but also reduced the number of metastatic pulmonary foci. Molecular mechanism(s) underlying the anti-breast cancer activities and inhibition of tumor metastasis of DET are under investigation.