Identification of a potent herbal molecule for the treatment of breast cancer

To determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER+)-MCF-7 and estrogen-receptor negative (ER-)-MDA 231 cells were treated with PDBD and the cell viability, apoptotic, cell cycle, Western blot and Promoter assays were performed.PDBD inhibits cell viability of ER+ and ER- BCa cells by inducing apoptosis without causing significant toxicity in normal breast epithelial cells. While dissecting the mechanism of action of PDBD on BCa, we found that PDBD inhibits Akt signaling and its downstream targets such as NF-κB activation, IAP proteins and Bcl-2 expression. On the other hand, activation of JNK/p38 MAPK-mediated pro-apoptotic signaling was observed in both ER+ and ER- BCa cells.These findings suggest that PDBD may have wide therapeutic application in the treatment of BCa.Patients with estrogen receptor-negative breast cancer (ER- BCa) have a median survival of 10–12 months when compared to patients with for ER-positive (ER+) BCa who have a median survival of 40–48 months [1]. Limited effectiveness of current chemotherapeutic drugs such as tamoxifen, paclitaxel and docetaxel, shows severe side effects in the BCa patients [2], these realities underscore the importance of identifying novel targeted therapies with minimal side effects to treat this deadly disease.Akt plays a major role in the regulation of cell survival, apoptosis, and oncogenesis [3]. Activation of Akt negatively regulates the programmed cell death signaling either by blocking or inhibiting the pro-apoptotic proteins such as BAD, Forkhead transcription factors and GSK-3β [3-5]. The observations from cell culture studies suggests that activation of Akt leads to the phosphorylation of IKK which in turn results in NF-κB activation and cell survival [6]. Akt regulates cell cycle by phosphorylating the cell cycle inhibitors p21 and p27 resulting in uncontrolled cell proliferation in various cell types [7-9]. Additionally, Akt increases cyclin D1 expression thereby aiding cancer cell