Journal
ONCOLOGY
Volume 76, Issue 2, Pages 91-100Publisher
KARGER
DOI: 10.1159/000188664
Keywords
Nicotinamide; Retinoic acid; Vitamin D-3; Cell differentiation; Arrest; Leukemia
Categories
Funding
- NIH (USPHS)
- NY STEM
- NATIONAL CANCER INSTITUTE [R01CA033505] Funding Source: NIH RePORTER
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Nicotinamide, the amide derivative of vitamin B 3, cooperates with retinoic acid ( RA), a form of vitamin A, and 1,25-dihydroxyvitamin D-3 (D3), to regulate cell differentiation and proliferation of human myeloblastic leukemia cells. In human myeloblastic leukemia cells, RA or D3 are known to cause MAPK signaling leading to myeloid or monocytic differentiation and G0 cell cycle arrest. In this process, RA or D3 induces the early expression of CD38, a receptor that causes ERK signaling and propels further differentiation. Our study demonstrates that nicotinamide in combination with RA or D3 affected induced expression levels of CD38, CD11b and CD14, suggesting a cooperative function of nicotinamide and RA or D3. Nicotinamide transiently retarded the initial RA- or D3- induced expression of CD38, which subsequently reached the same nearly 100% expression. Nicotinamide induced ERK activation and further enhanced the RA- induced ERK activation, but the D3- induced ERK activation was diminished by nicotinamide, although levels still exceeded those induced by RA, suggesting lineage-specific nicotinamide responses. Nicotinamide enhanced both RA- and D3-induced CD11b expression, inducible oxidative metabolism, and G0 cell cycle arrest, accelerating their induced occurrence in all instances. Consistent with this, the RA- or D3-induced downregulation of PARP was enhanced by nicotinamide. Nicotinamide thus regulated RA- or D3-induced differentiation and G0 arrest, causing a transient delay in certain early aspects of the progression to terminal differentiation but ultimately accelerating the occurrence of terminally, functionally differentiated G0 cells. Copyright (C) 2009 S. Karger AG, Basel
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