Cytostatic activity of coumarin metabolites and derivatives in the B16-F10 murine melanoma cell line.
Coumarin has antitumour effects in vivo and cytostatic effects in vitro. Its half-life in humans is short (1-1.5 h) and the monohydroxylated biotransformation products have significantly longer half-lives. One or several of these products may thus be responsible for the antitumoral effects. We have assayed the in vitro cytostatic activity of five monohydroxylated coumarins (3-, 4-, 6-, 7- and 8-monohydroxycoumarin), their acetates and methyl-ethers. Murine melanoma cells (cell line B16-F10) and murine fibroblasts (B82) were exposed to the test compounds at concentrations between 10 and 160 microg/ml. The cytostatic effects were estimated by reduction of the tetrazolium dye MTT. In the melanoma cells, some of the compounds inhibited growth after exposure for 1 day. In contrast, coumarin inhibited growth to a smaller extent, and only after exposure for 3 days. The most active compounds (3-acetoxycoumarin, 4-methoxycoumarin and 6-hydroxycoumarin), as well as coumarin, were also assayed in murine fibroblasts. The cytostatic effects of 4-methoxycoumarin and 6-hydroxycoumarin were less pronounced in fibroblasts than in melanoma cells. Our observations suggest that these compounds may have a greater therapeutic margin.
Jiménez-Orozco
F A
FA
Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexíco D.F. alejo@servidor.unam.mx
Molina-Guarneros
J A
JA
Mendoza-Patiño
N
N
León-Cedeño
F
F
Flores-Pérez
B
B
Santos-Santos
E
E
Mandoki
J J
JJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts; D020128:Inhibitory Concentration 50; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014468:Umbelliferones / Q000494:pharmacology
D000970:Antineoplastic Agents; D003374:Coumarins; D014468:Umbelliferones; C031477:7-hydroxycoumarin