1-Methylnicotinamide stimulates cell growth and inhibits hemoglobin synthesis in differentiating murine erythroleukemia cells.
Exposure of murine erythroleukemia cells (MELCs) to nicotinamide (NA) or its synthetic analog N'-methylnicotinamide (N'-MN) reduces cell growth and induces terminal differentiation, marked by increased heme and globin accumulation. On the contrary, 1-methylnicotinamide (1-MN), the primary metabolite of excess NA, was found to stimulate cell growth and reduce spontaneous differentiation of cultured MELCs. Log phase MELCs exhibited up to 50% higher cell density above untreated cells when cultured for up to 96 h with 2.5 mM 1-MN. When combined with NA or several chemically-unrelated inducers of hemoglobin synthesis in cultured MELCs, 1-MN reduced the globin mRNA levels and heme accumulation by 40-80%. 1-MN was able to inhibit heme production if present during only the first 24-48 h after NA exposure. Pre-treatment with 1-MN could not confer resistance of cells to effects of NA, suggesting the inhibition is reversible. Commitment to differentiate in semisolid medium by the most potent inducer, 5mM N'-MN, was inhibited up to 95% by 2.5mM concentrations of 1-MN. It appears that 1-MN has opposing effects on growth and induction of differentiation than those seen in MELC cultures exposed to NA or N'-MN.
Kuykendall
Jim R
JR
Raabe College of Pharmacy, Department of Pharmaceutical and Biomedical Sciences, Ohio Northern University, 525 South Main, Ada, OH 45810, USA. Jim.ToxiGen@gmail.com
Cox
Ray
R
Kinder
David
D
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects*; D005914:Globins / Q000235:genetics / Q000378:metabolism; D006454:Hemoglobins / Q000096:biosynthesis*; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D051379:Mice; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors