Different modulation of TRAIL-induced apoptosis by inhibition of pro-survival pathways in TRAIL-sensitive and TRAIL-resistant colon cancer cells.
Epithelial cells can be manipulated to undergo apoptosis depending on the balance between pro-survival and apoptotic signals. We showed that TRAIL-induced apoptosis may be differentially regulated by inhibitors of MEK ERK (U0126) or PI3K/Akt (LY294002) pathway in TRAIL-sensitive (HT-29) and TRAIL-resistant (SW620) human epithelial colon cancer cells. U0126 or LY294002 significantly enhanced TRAIL-induced apoptosis in HT-29 cells, but not in SW620 cells. We report a different regulation of the level of an anti-apoptotic Mcl-1 protein under MEK/ERK or PI3K/Akt pathway inhibition and suggest the mechanisms involved. A special attention was paid to the role of the ERK1/2, Akt, and glycogen synthase kinase 3beta.
Vaculová
Alena
A
Laboratory of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 612 65 Brno, Czech Republic.
Hofmanová
Jirina
J
Soucek
Karel
K
Kozubík
Alois
A
D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D019073:HT29 Cells; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D053538:Keratin-18; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; D011065:Poly(ADP-ribose) Polymerases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D038362:Glycogen Synthase Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D053181:Caspase 8