The Notch ligand, Delta-1, alters retinoic acid (RA)-induced neutrophilic differentiation into monocytic and reduces RA-induced apoptosis in NB4 cells.
Effects of Notch activation on retinoic acid (RA)-induced differentiation and apoptosis were investigated. NB4, an acute promyelocytic leukemia (APL) cell line, undergoes neutrophilic differentiation and apoptosis by RA. Notch activation induced by a recombinant Notch ligand, Delta-1, did not affect the growth by itself. Treatment with RA plus Delta-1 made part of NB4 cells monocyte-like shaped and reduced the apoptosis. Similar phenomenon was also observed in primary APL cells. RA treatment induced cleavage of caspase-8 and PARP in NB4. Delta-1 suppressed the RA-induced cleavage of them, which may be a possible mechanism through which Delta-1 suppressed the RA-induced apoptosis.
Murata-Ohsawa
Mai
M
Department of Laboratory Medicine, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-Ku, Tokyo 113-8519, Japan.
Tohda
Shuji
S
Kogoshi
Hanae
H
Sakano
Seiji
S
Nara
Nobuo
N
D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism* / Q000494:pharmacology*; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D051880:Receptors, Notch; D014212:Tretinoin / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology
D015703:Antigens, CD; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; C064045:delta protein; D014212:Tretinoin; D011065:Poly(ADP-ribose) Polymerases; D016186:Receptor, Macrophage Colony-Stimulating Factor; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases