Cytotoxicity of mebendazole against established cell lines from the human, rat, and mouse liver.
The direct cytotoxicity of mebendazole (MBZ) was investigated by using cell lines derived from human, mouse and rat liver. It was demonstrated that Chang liver cells (derived from human liver) were more sensitive to the cytotoxic effects of MBZ than the other two cell lines. Longer incubation of the cells with MBZ resulted in stronger toxicity, and the cytotoxicity was dependent on the MBZ concentration above a certain threshold value (0.25-0.50 mg/l in a 42-h culture). Inhibition of the proliferation of Chang liver cells by MBZ was detected at a concentration of 0.008 mg/l, a lower concentration than that having a cytotoxic effect. The other two cell lines were less sensitive to the inhibitory effect of MBZ. Proliferation of human mononuclear cells following stimulation by phytohemagglutinin (PHA) was inhibited by MBZ, and this inhibition was more extensive than that of cells stimulated with whole formalin-treated Pseudomonas aeruginosa. It is suggested that dividing cells may be more sensitive to MBZ cytotoxicity. This anti-proliferative effect may be related to its clinically known side effects, such as hepatotoxicity and bone marrow suppression.
Higa
F
F
First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Kitsukawa
K
K
Gaja
M
M
Tateyama
M
M
Shikiya
K
K
Shigeno
Y
Y
Kinjo
F
F
Saito
A
A
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003864:Depression, Chemical; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008463:Mebendazole / Q000633:toxicity*; D051379:Mice; D051381:Rats
D008463:Mebendazole