The anti-proliferative effects of nicotinamide and 3-aminobenzamide on human smooth muscle cells in vitro.
The proliferation of cultured human arterial smooth muscle cells (HASMC) was suppressed by nicotinamide and its analogue, 3-aminobenzamide, in a concentration-dependent manner, based on cell count and [3H]thymidine incorporation into DNA. The addition of 10 and 15 mM nicotinamide, or 6 mM 3-aminobenzamide, to HASMC, for 96 h, resulted in a 19.3%, 44% and 41.5% reduction of cell growth and inhibition of DNA synthesis. Since c-myc protooncogene expression has previously been correlated with cell proliferation, the steady state level of its mRNA was determined in control and treated HSMC by Northern analysis, following a 1 h treatment with the respective chemicals. Whereas c-myc mRNA was suppressed by nicotinamide in proportion to its ability to reduce HASMC growth, down regulation of c-myc by 3-aminobenzamide was much less than the observed antiproliferative effect. These results suggest that the growth regulatory properties of nicotinamide and 3-aminobenzamide in HASMC are probably unrelated to their activity in controlling c-myc gene expression.
Cui
Y
Y
Department of Experimental Pathology, New York Medical College, Valhalla 10595.
An
S
S
Jabr
S
S
Maturana
J A
JA
Wu
J M
JM
Gutstein
W H
WH
D001013:Aorta, Thoracic / Q000166:cytology; D001549:Benzamides / Q000494:pharmacology*; D015152:Blotting, Northern; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc; D006801:Humans; D008854:Microscopy, Electron; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D013936:Thymidine / Q000378:metabolism
D001549:Benzamides; D012333:RNA, Messenger; D009536:Niacinamide; C025160:3-aminobenzamide; D004247:DNA; D013936:Thymidine