title: Cytotoxicity of TRAIL/anticancer drug combinations in human normal cells.
abstract: 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.
authors: 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.
authors: Olivier
authors: O
authors: Meurette
authors: Anne
authors: A
authors: Fontaine
authors: Amelie
authors: A
authors: Rebillard
authors: Gwenaelle
authors: G
authors: Le Moigne
authors: Thierry
authors: T
authors: Lamy
authors: Dominique
authors: D
authors: Lagadic-Gossmann
authors: Marie-Therese
authors: MT
authors: Dimanche-Boitrel
mesh_terms: 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*
chemical_list: D000970:Antineoplastic Agents; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human