Deoxyelephantopin exhibits potent effects against mammary 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 indications such as antitumor and anti-inflammation. The most abundant sesquiterpene lactone, namely deoxyelephantopin (DET), with potent anti-tumor cell activity was isolated from E. scaber extracts in this study. DET was observed to significantly inhibit colony formation, cell proliferation, migration and invasion of TS/A mammary cancer cells at effective concentrations ≤2µg/ml. DET could also time-dependently induce cell cycle arrest at G₂/M and cause a marked increase of apoptosis in TS/A cells. Caspases-mediated cascade events on lamin A and poly (ADP-ribose) polymerase cleavage were observed in DET-treated TS/A cells. DET also increased c-Jun phosphorylation and protein expression levels, which was blocked by the specific JNK inhibitor SP600125. Moreover, TNF-α induced NF-κB activation and p65 translocation was also abolished by DET. The in vivo TS/A tumor model in syngeneic BALB/c mouse further demonstrated that DET possessed profound effects on TS/A tumor growth as observed with a smaller tumor size in the DET-treated mice than that of Taxol-treated mice (T/C values=50% vs. 73%). In lung metastasis experiments, DET pretreatment could not only reduce the number of metastatic pulmonary foci but also significantly prolong the overall survival rate in test animals compared to the vehicle control group. Comparative proteomic approaches are employed to investigate the important biomarkers in TS/A cells in response to DET treatment. Taken together, this study suggests that DET has a therapeutic potential for anti-breast cancer.