Premium
Effects of BITC on TRAIL Sensitization in Human Pancreatic Adenocarcinomas
Author(s) -
Wicker Christina Ann,
KulkarniDatar Kashmira,
Srivastava Sanjay K.,
Brown Thomas L.
Publication year - 2008
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.22.1_supplement.1238.7
Subject(s) - apoptosis , pancreatic cancer , cancer research , adenocarcinoma , biology , cancer , medicine , genetics
Pancreatic adenocarcinoma is an aggressive cancer with a greater than 95 % mortality rate and an average survival period of 4–6 months after diagnosis. Treatment options for pancreatic cancer are limited. Chemotherapeutic resistance has been associated with mutations within codon 12 of the K‐Ras gene (K‐Ras 12). These mutations are present in over 90 % of all pancreatic adenocarcinomas and leave Ras in a constitutively‐active state leading to continual cellular proliferation. Benzyl isothiocyanate (BITC) is a component of cruciferous vegetable extract, and a reported cell cycle inhibitor. TNF‐related apoptosis inducing ligand (TRAIL) is a novel cytokine, whose receptor is highly expressed on tumor cells but generally absent on normal cells. Thus, TRAIL can preferentially target tumor cells to induce apoptosis while leaving non‐tumor cells relatively unharmed. Our study determined if TRAIL resistance in pancreatic adenocarcinoma with codon 12 K‐Ras mutations can be overcome by first sensitizing the cells using BITC. Western blot analysis revealed activation of early apoptotic pathways but failure to activate later apoptotic pathways resulting in little increase in apoptosis between TRAIL alone and BITC with TRAIL. These results reveal the need to further study alternative survival mechanisms that contribute to chemotherapeutic resistance.