Abstract 3207: Curcumin induces pancreatic cancer cell death by targeting IAPs

Background Pancreatic cancer has among the highest mortality rates compared to other cancer types, with 94% of patients dying within five years of diagnosis. Contributing to the high mortality rate, patients with pancreatic cancer do not present significant symptoms until the disease is advanced. Moreover, treatment strategies have not improved substantially over the last decade. For this reason, a recent trend has led toward focusing on the use of herb-derived compounds, such as curcumin (turmeric derivative), to explore alternative treatments that will improve current pancreatic cancer therapy. Objective The objectives of this study were (1) to determine the effects of curcumin on pancreatic cancer cell metabolism, viability, cell cycle and morphology, and (2) to determine the mechanism by which curcumin induces cell death in pancreatic cancer cells by analyzing intracellular expression levels of inhibitor of apoptosis proteins (IAPs). Design/method Pancreatic adenocarcinoma cell lines (Panc-1 and MiaPaCa-2) were used to assess the effects of curcumin in pancreatic cancer. Effects on metabolism, viability and cell cycle were assayed by Alamar Blue, Trypan Blue and Propidium Iodide (PI) staining/flow cytometry (FACSCalibur). Morphological imaging was performed using Hoffman Modulation microscopy. Apoptosis was detected by Annexin V/PI flow cytometry (MACSQuant) and the expression of IAPs was assessed by Western blot. Results These data show that curcumin decreases pancreatic cancer cell metabolism and viability. Cell cycle stages were arrested in pancreatic cancer cells treated with curcumin compared to the non-treated controls. Apoptotic cells were detected by microscopy and confirmed by Annexin V/PI staining with subsequent flow cytometry analysis. IAPs levels are reduced in pancreatic cancer cell lines treated with curcumin compared to non-treated controls. Conclusion These results demonstrate that pancreatic adenocarcinoma cell lines are sensitive to curcumin treatment. Moreover, curcumin9s possible mechanism of action is inducing apoptosis by targeting IAPs. Collectively, these data suggest a potential role for curcumin in pancreatic cancer therapy. Citation Format: Carlos J. Diaz Osterman, Malyn May Asuncion Valenzuela, Heather R. Ferguson Bennit, Salma Khan, Nathan R. Wall. Curcumin induces pancreatic cancer cell death by targeting IAPs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3207. doi:10.1158/1538-7445.AM2014-3207