Lobenzarit disodium (CCA) inhibits the proliferation of human endothelial cells and the activity of DNA polymerase alpha.
N-(2)-Carboxyphenyl-4-chloroanthranilic acid disodium [Lobenzarit disodium (CCA)] is widely used for the treatment of patients with RA in Japan; however, the pharmacological mechanism of the compound is still unclear. In this report, the effect of CCA on the proliferation and DNA synthesis of endothelial cells was examined. CCA inhibited DNA synthesis in endothelial cells at a rather lower concentration than that in fibroblasts and HeLa cells. The DNA polymerase alpha activity was inhibited by CCA at a lower concentration than E. coli DNA polymerase I and avian myeloblastosis virus reverse transcriptase. Thus, CCA is a potent inhibitor of DNA polymerase alpha and this inhibitory effect could cause the inhibition of endothelial cell proliferation, which may be related to the therapeutic and pharmacological mechanisms of CCA.
Takeuchi
F
F
Department of Internal Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Kosuge
E
E
Hashimoto
Y
Y
Matsuta
K
K
Hanaoka
F
F
Tanimoto
K
K
Ito
K
K
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D009189:Avian Myeloblastosis Virus / Q000201:enzymology; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018894:Reverse Transcriptase Inhibitors; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018894:Reverse Transcriptase Inhibitors; D062367:ortho-Aminobenzoates; D004247:DNA; C015735:lobenzarit; D004257:DNA Polymerase II