Abstract 4596: Phenethyl isothiocyanate inhibits growth of MIAPaca2 human pancreatic cancer xenograft in vivo in association with apoptosis induction

Abstract

Abstract Pancreatic cancer is the fourth leading cause of cancer-related deaths in the U.S. with a 5-year survival rate of less than 5%. Low survival rate for patients with pancreatic cancer points towards an increased need for novel chemoprevention, early detection, and therapeutic strategies for this disease. This study was undertaken to determine the efficacy of phenethyl isothiocyanate (PEITC), a naturally occurring isothiocyanate found in cruciferous vegetables, against pancreatic cancer cells in vitro and in vivo. Exposure of human pancreatic cancer cells (MIAPaca2, PL-45, and BxPC3) to PEITC resulted in growth inhibition, which was accompanied by apoptotic cell death regardless of the K-ras status. Apoptotic cell death by PEITC treatment was characterized by an increase in cytoplasmic histone-associated DNA fragmentation and enrichment of sub-diploid fraction. PEITC-induced apoptosis correlated with induction of pro-apoptotic protein Bak, down-regulation of anti-apoptotic proteins Bcl-2 and Bcl-xL, and cleavage of caspase-3 and PARP. Oral administration of 12 µmol PEITC/mouse (five times per week) significantly retarded the growth of MIAPaca2 xenografts in male nude mice without causing weight loss or any other signs of toxicity. PEITC administration significantly reduced proliferation as determined by PCNA and Ki-67 stainings and increased apoptosis in tumors as shown by TUNEL assay. In conclusion, the present study demonstrates, for the first time, that PEITC administration retards the growth of human pancreatic cancer xenografts by inducing apoptotic cell death. The present study provides pre-clinical evidence for development of PEITC as a chemopreventive agent for pancreatic cancer. This investigation was supported in part by the Wayne Fusaro Pancreatic Cancer Research Fund (DCW), the Shirley Hobbs Martin Memorial Fund (REB), and the NCI grants CA101753 and CA113363 (SVS). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4596. doi:10.1158/1538-7445.AM2011-4596