In vitro and In vivo Antitumor Effects of Deoxyelephantopin on Human Breast Cancer Cells

Abstract

Breast cancer is one of the most common cancers in women, and a leading cause of death worldwide. It is often highly resistant to chemotherapy, and there is often no effective cure for patients in the advanced stages of the disease. In this study, we evaluated the effect of deoxyelephantopin (DET), a phytocompound extracted from Elephantopus scaber L. (Asteraceae) for possible anti-tumor activities in the human breast cancer cell-line MDA-MB-231. Cell-apoptosis assay showed that DET treatment was able to effectively suppress the growth of test tumor cells in vitro. In addition, DET treatment significantly decreased expression level of transforming growth factor-beta (TGF-β), effectively inhibited cell growth by inducing G2-M phase cell cycle arrest and apoptosis, and reduced the clonogenicity in a concentration-dependent manner in MDA-MB-231 cells. DET also significantly inhibited the invasion and migration of test breast tumor cells. The effect of DET on suppression of NF-κB, via activation by TNF-α, was examined using electrophoretic mobility shift analysis (EMSA). Decreased levels of expression of phospho-NF-κB and the downstream molecules of the NF-κB signaling pathway, including survivin, Bcl-2, MMP-9 and VEGF, were observed in DET-treated MDA-MB-231 cells. In vivo, DET significantly inhibited tumor growth and the myeloid derived suppressor cell (MDSC) population in nude mice. Taken together, our findings suggest that DET may warrant a further systematic investigation for potential applications in the chemoprevention or control of breast cancers. Keywords: Deoxyelephantopin (DET), Elephantopus scaber, Asteraceae, anticancer