TRAIL (TNF-related apoptosis-inducing ligand) induces necrosis-like cell death in tumor cells at acidic extracellular pH.
How tumor microenvironment, more specifically low extracellular pH (6.5), alters cell response to TNF-related apoptosis-inducing ligand (TRAIL)-based cancer therapy has yet to be determined. The aim of the current work was to test the effect of acidic extracellular pH on TRAIL-induced cell death in human HT29 colon carcinoma and HepG2 hepatocarcinoma cell lines as well as in human primary hepatocytes. We found an increase in TRAIL sensitivity at low extracellular pH, which is partially inhibited by Bcl-2 expression in HT29 cells. At low extracellular pH, TRAIL induced a new form of cell death, sharing necrotic and apoptotic features in tumor cells. By contrast, human primary hepatocytes were resistant to TRAIL-induced cell death even at acidic extracellular pH.
Meurette
Olivier
O
INSERM U620, Faculté de Pharmacie, Université Rennes 1, 2 av Prof Léon Bernard, 35043 Rennes cedex, France.
Huc
Laurence
L
Rebillard
Amelie
A
Le Moigne
Gwenaelle
G
Lagadic-Gossmann
Dominique
D
Dimanche-Boitrel
Marie-Therese
MT
D006528:Carcinoma, Hepatocellular; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008113:Liver Neoplasms; D009336:Necrosis; D009369:Neoplasms; D053221:TNF-Related Apoptosis-Inducing Ligand
D053221:TNF-Related Apoptosis-Inducing Ligand