Role of MAPKs and NF-kappaB in diosgenin-induced megakaryocytic differentiation and subsequent apoptosis in HEL cells.
Megakaryocytopoiesis is characterized by progressive polyploidization and acquisition of megakaryo-cytic markers. MAPK pathways play a key role during megakaryocytic differentiation of megakaryocyte precursors or leukemic cells. Apoptosis is the physiological fate of normal megakaryocyte after differentiation and maturation. The aim of this study was to investigate the signaling pathways involved in diosgenin-induced differentiation and the fate of diosgenin-differentiated HEL cells. The present report shows that diosgenin induced megakaryocytic differentiation of HEL cells through a combined activation of ERK and inhibition of the p38 MAPK pathways. Inhibition of ERK activation by a MEK inhibitor abrogated diosgenin-induced differentiation. Afterwards, differentiated cells showed a marked inhibition of expression of survival factors NF-kappaB, Akt and Bcl-xL and activation of caspase-3 together with PARP cleavage leading to apoptotic death of diosgenin-differentiated cells.
Leger
David Y
DY
Laboratoire de Biochimie, UPRES EA 1085, Faculté de Pharmacie, 87025 Limoges Cedex, France.
Liagre
Bertrand
B
Beneytout
Jean-Louis
JL
D017209:Apoptosis / Q000235:genetics*; D002454:Cell Differentiation; D004144:Diosgenin / Q000494:pharmacology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D008533:Megakaryocytes / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D020929:Mitogen-Activated Protein Kinase Kinases; D004144:Diosgenin