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TRAIL (TNF‐Related Apoptosis‐Inducing Ligand) Induces Necrosis‐Like Cell Death in Tumor Cells at Acidic Extracellular pH
Author(s) -
MEURETTE OLIVIER,
HUC LAURENCE,
REBILLARD AMELIE,
MOIGNE GWENAELLE,
LAGADICGOSSMANN DOMINIQUE,
DIMANCHEBOITREL MARIETHERESE
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1352.018
Subject(s) - extracellular , apoptosis , programmed cell death , tumor necrosis factor alpha , chemistry , microbiology and biotechnology , necrosis , cell culture , cell , cancer cell , extracellular matrix , cancer research , biology , biochemistry , cancer , immunology , genetics
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.