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Effect of Phenethyl Isothiocyanate on p21 Waf1/Cip1 Regulation of Cell Cycle Arrest in Pancreatic Cancer Cells
Author(s) -
Brebberman Ryan,
Stan Silvia
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb294
Subject(s) - phenethyl isothiocyanate , pancreatic cancer , cancer research , cancer , downregulation and upregulation , cell cycle , cyclin dependent kinase 1 , tumor suppressor gene , cancer cell , cruciferous vegetables , medicine , biology , carcinogenesis , biochemistry , gene
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 p21 Waf1/Cip1 . PEITC induced a dose‐dependent upregulation in p21 Waf1/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 p21 Waf1/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).