Breast cancer is the most common cancer and the leading cause of cancer related deaths amongst women in the United States. In 15-20% of... Show moreBreast cancer is the most common cancer and the leading cause of cancer related deaths amongst women in the United States. In 15-20% of patients with breast cancer, patients do not express steroid receptors(ER/PR) and do not have amplification of HER2. This condition is called triple negative breast cancer (TNBC). Patients with TNBC have poor prognosis. No molecular targeted therapies are available to treat TNBC. Anthracyclines and taxane based therapies are effective with limited success, and are often toxic. As TNBC cells overexpress Epidermal Growth Factor Receptor (EGFR), it provides an attractive molecular tool for the targeted therapy. Deguelin, a rotenoid isolated from an African plant, Mundulea sericea has been shown to inhibit growth of various experimental cancers. Deguelin is a well known inhibitor of pAKT, a downstream target of EGFR. In this study we evaluated the effect of deguelin and its mechanism of anticancer action in triple negative human breast cancer cell lines. Deguelin inhibited cell proliferation of MDA-MB-231, MDA-MB-468, BT-549, and BT- 20 in a dose and time-dependent manner. Western blots and immunofluorescence analyses suggested that the effect of Deguelin is mediated through inhibition of Receptor Tyrosine Kinases (EGFR, c-Met) and its downstream molecular targets, Our results show that deguelin treatment reduces the expression of pERK (p44/42) (Thr202/Tyr204), pAKT (ser473), c-Myc, pSTAT3 (Tyr705) and survivin in a dose and time dependent manner in MDA-MB-231, MDA-MB-468 human breast cancer cells. In conclusion, results from this study suggest that Deguelin may be of potential therapeutic value in treatment of triple negative breast cancers. M.S. in Biology, December 2012 Show less
