Activation and Role of MAP Kinases in 15d-PGJ2-Induced Apoptosis in the Human Pancreatic Cancer Cell Line MIA PaCa-2

Koji Hashimoto, Buckminster J. Farrow, B. Mark Evers

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Aim: We have previously reported that 15-deoxy-Δ 12,14-prostaglandin J2 (15d-PGJ2), a potent ligand for peroxisome proliferator-activated receptor γ (PPARγ), induces caspase-mediated apoptosis in human pancreatic cancer cell lines. Mitogen-activated protein kinases (MAPKs) are known to regulate apoptosis in various cancers. The purpose of this study was to investigate the role of MAPKs (ERK, JNK, and p38) in 15d-PGJ2-induced pancreatic cancer cell apoptosis. Methodology: The effect of 15d-PGJ2 on MAPK activity was investigated by kinase assays using the human pancreatic cancer cell line MIA PaCa-2. Western blot analysis was performed to analyze phosphorylation of MAPKs, activation of caspases and poly ADP-ribose polymerase (PARP) cleavage. Apoptosis was evaluated by caspase-3 enzymatic activity and DNA fragmentation assay. Results: 15d-PGJ2 activated all 3 MAPKs in a dose- and time-dependent fashion. SB202190, an inhibitor of p38, prevented 15d-PGJ 2-induced activation of caspase-8, -9, and -3 and significantly decreased apoptosis. This effect was potentiated by SP600125, an inhibitor of JNK, although SP600125 alone had no significant effect on 15d-PGJ 2-induced apoptosis. In contrast, PD98059, an inhibitor of MEK, significantly increased sensitivity to 15d-PGJ2-induced apoptosis. Conclusions: 15d-PGJ2 stimulates proapoptotic and antiapoptotic MAPK pathways. Sensitivity to 15d-PGJ2-induced apoptosis is increased by ERK inhibition but decreased by inhibition of p38.

Original languageEnglish
Pages (from-to)153-159
Number of pages7
JournalPancreas
Volume28
Issue number2
DOIs
StatePublished - Mar 2004

Keywords

  • 15d-PGJ
  • MAPK
  • MIA PaCa-2
  • PPARγ
  • Pancreatic cancer

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Fingerprint

Dive into the research topics of 'Activation and Role of MAP Kinases in 15d-PGJ2-Induced Apoptosis in the Human Pancreatic Cancer Cell Line MIA PaCa-2'. Together they form a unique fingerprint.

Cite this