A new anti-inflammatory leucine derivative, NPC-15669, inhibits growth of cultured human aortic smooth muscle cells.
We have observed that NPC-15669, a leucine derivative with anti-inflammatory activity, reduced the proliferation of human aortic smooth muscle cells (HASMCs) in culture. We used a colorimetric assay and tritiated thymidine to measure the cell density and proliferation of HASMC cultures treated with this agent. We also studied the effect of NPC-15669 on the proliferation and migration of human aortic endothelial cells (HAECs). Subconfluent HASMC cultures were growth arrested for 2 days. On the third day, growth was stimulated with either growth media (medium M199 containing 10% fetal bovine serum [FBS]), human platelet-derived growth factor (hPDGF), or fibroblast growth factor (FGF) in the absence or presence of NPC-15669 (0.1-50 microM). Regardless of the stimulating agent for HASMCs (FBS, hPDGF, or FGF), NPC-15669 at concentrations of 10-25 microM caused a significant reduction in thymidine incorporation (36.7% and 77.2% in 10 microM and 25 microM, respectively; p < 0.005) and cell density (25-87%, p < 0.001) compared with control. NPC-15669 did not, however, have an effect on the rate of proliferation or migration of HAECs, even at concentrations up to 50 microM. Two other anti-inflammatory agents, aspirin and dexamethasone, caused substantially and significantly less inhibition, even at high concentrations (50 and 25 microM, respectively). This study demonstrates that in vitro, NPC-15669 significantly inhibits HASMC proliferation but has no effect on proliferation or migration of HAECs.
Bennett
R L
RL
Division of Cardiology, UCLA School of Medicine 90024-1679.
Navab
M
M
Demer
L L
LL
Fogelman
A M
AM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; C071244:N-(9H-(2,7-dimethylfluoren-9-ylmethoxy)carbonyl)leucine; D003907:Dexamethasone; D007930:Leucine; D001241:Aspirin; D013936:Thymidine