Inhibition of microtubule assembly is a possible mechanism of action of mitoxantrone.
We have found that mitoxantrone can inhibit the polymerization of brain tubulin in a dose dependent manner. MXT had relatively high affinity for tubulin but had no appreciable effect on tubulin associated guanosine-triphosphatase (GTPase) activity nor could it compete with vinblastine (VB) and colchicine (Col) for tubulin binding sites. Furthermore, MXT (0.1-10 microM) is antiproliferative to cold-treated (0 degree C) epithelial cells after only brief exposure (30 min). These results indicated that MXT is a microtubule inhibitory agent and can exert its anticellular effect through modulation of microtubule assembly.
Department of Medical Research, Veterans General Hospital, Taipei, Republic of China.
C K
CK
Ho
S L
SL
Law
H
H
Chiang
M L
ML
Hsu
C C
CC
Wang
S Y
SY
Wang
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D003078:Colchicine / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007624:KB Cells; D008870:Microtubules / Q000187:drug effects* / Q000648:ultrastructure; D008942:Mitoxantrone / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology
D014404:Tubulin; D014747:Vinblastine; D008942:Mitoxantrone; D020558:GTP Phosphohydrolases; D003078:Colchicine