Inhibition of the ERK pathway promotes apoptosis induced by 2-chloro-2'-deoxyadenosine in the B-cell leukemia cell line EHEB.
2-Chloro-2'-deoxyadenosine (CdA) is a nucleoside analogue active in B-cell chronic lymphocytic leukemia (B-CLL). Although the mechanism of action of CdA has been extensively investigated in leukemic cells, the possibility that this nucleoside analogue interacts with the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway has never been explored. In this study, we show that CdA, at concentrations close to the IC50, activated the ERK pathway in the B-cell line EHEB. Because activation of this pathway is assumed to exert anti-apoptotic effect, we combined CdA with inhibitors of the ERK pathway. The latter were found to enhance CdA-induced apoptosis. These results suggest that the efficacy of CdA could be strengthened by combination with inhibitors of the ERK pathway.
Smal
C
C
Laboratory of Physiological Chemistry, Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Brussels, Belgium.
Lisart
S
S
Ferrant
A
A
Bontemps
F
F
van den Neste
E
E
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D017338:Cladribine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000201:enzymology*; D010766:Phosphorylation
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D017338:Cladribine; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3