Effect of Phenethyl Isothiocyanate on p21Waf1/Cip1 Regulation of Cell Cycle Arrest in Pancreatic Cancer Cells

Abstract

Pancreatic cancer continues to be a disease with a dismal prognosis primarily due to diagnosis occurring later in the progression of the disease. Once at an advanced stage, treatment of the tumor through conventional therapies often proves ineffective prompting the need for preventive strategies for this cancer. Phenethyl isothiocyanate (PEITC) is a natural compound found in cruciferous vegetables such as watercress. In this study we show that PEITC inhibited proliferation of MIAPaca2 and PL45 pancreatic cancer cells, and induced mitotic arrest within 8 and 16 h of treatment as evidenced by a dose‐dependent increase in expression of phospho‐histone H3 (Ser10), a marker of cells undergoing mitosis. Treatment with PEITC led to phosphorylation of p53 tumor suppressor protein, and modulated the p53‐inducible gene product p21Waf1/Cip1. PEITC induced a dose‐dependent upregulation in p21Waf1/Cip1 tumor suppressor protein in MIAPaca2 and PL45 pancreatic cancer cells within 4 and 8 h of treatment. In conclusion, the growth inhibitory effect of PEITC was associated with activation of p53, upregulation of cyclin‐dependent kinase inhibitor p21Waf1/Cip1, and induction of mitotic arrest in pancreatic cancer cells, and warrants further investigation of PEITC as a chemopreventive agent for pancreatic cancer. This study was supported in part by PUCCR ACS IRG#58‐006‐53 (awarded to SDS).