Fa. Jimenez-orozco et al., Cytostatic activity of coumarin metabolites and derivatives in the B16-F10murine melanoma cell line, MELANOMA RE, 9(3), 1999, pp. 243-247
Coumarin has antitumour effects in vivo and cytostatic effects in vitro. It
s half-life in humans is short (1-1.5 h) and the monohydroxylated biotransf
ormation products have significantly longer half-lives. One or several of t
hese 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-ethe
rs. Murine melanoma cells (cell line B16-F10) and murine fibroblasts (B82)
were exposed to the test compounds at concentrations between 10 and 160 mu
g/ml. The cytostatic effects were estimated by reduction of the tetrazolium
dye MTT. In the melanoma cells, some of the compounds inhibited growth aft
er 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-ac
etoxycoumarin, 4-methoxycoumarin and 6-hydroxycoumarin), as well as coumari
n, were also assayed in murine fibroblasts. The cytostatic effects of 4-met
hoxycoumarin and 6-hydroxycoumarin were less pronounced in fibroblasts than
in melanoma cells. Our observations suggest that these compounds may have
a greater therapeutic margin. (C) 1999 Lippincoti Williams & Wilkins.