Cytotoxicity of TRAIL/anticancer drug combinations in human normal cells.
TRAIL (TNF-alpha-Related Apoptosis-Inducing Ligand) is a promising anticancer agent. In fact, it induces apoptosis in cancer cells and not in most normal cells. Nevertheless, certain cancer cells are resistant to TRAIL-induced apoptosis and this could limit TRAIL's efficiency in cancer therapy. To overcome TRAIL resistance, a combination of TRAIL with chemotherapy could be used in cancer treatment. However, sensitivity of human normal cells to such combinations is not well known. We showed in this study that TRAIL/cisplatin, in contrast to TRAIL/5-fluorouracil, was toxic toward human primary hepatocytes and resting lymphocytes. Furthermore, both combinations are toxic toward PHA-IL2-activated lymphocytes. In contrast, freshly isolated neutrophils are resistant to TRAIL in combination or not with anticancer drugs.
Meurette
Olivier
O
INSERM U620, IFR140, Faculté de Pharmacie, Université de Rennes 1, 2 avenue Prof. Léon Bernard, 35043 Rennes cedex, and Département d'Hématologie, Hôpital Pontchaillou, France.
Fontaine
Anne
A
Rebillard
Amelie
A
Le Moigne
Gwenaelle
G
Lamy
Thierry
T
Lagadic-Gossmann
Dominique
D
Dimanche-Boitrel
Marie-Therese
MT
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage / Q000494:pharmacology*
D000970:Antineoplastic Agents; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human