Microtubule disassembly and inhibition of mitosis by a novel synthetic pharmacophore.
Microtubule drugs, which block cell cycle progression through mitosis, have seen widespread use in cancer chemotherapies. Although microtubules are subject to regulation by signal transduction mechanisms, their pharmacological modulation has so far relied on compounds that bind to the tubulin subunit. A new microtubule pharmacophore, diphenyleneiodonium, causing disassembly of the microtubule cytoskeleton is described here. Although this synthetic compound does not affect the assembly state of purified microtubules, it profoundly suppresses microtubule assembly in vivo, causes paclitaxel-stabilized microtubules to cluster around the centrosomes, and selectively disassembles dynamic microtubules. Similar to other microtubule drugs, this new pharmacophore blocks mitotic spindle assembly and mitotic cell division.
Scaife
Robin M
RM
Laboratory for Cancer Medicine, Western Australian Institute for Medical Research, Centre for Medical Research, The University of Western Australia, Western Australia, Australia. rscaife@cyllene.uwa.edu.au
D000818:Animals; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects*; D006131:Growth Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects*; D050258:Mitosis Modulators / Q000138:chemical synthesis / Q000494:pharmacology*; D009861:Onium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D049468:Prometaphase / Q000187:drug effects*; D051381:Rats; D050257:Tubulin Modulators / Q000494:pharmacology*
D006131:Growth Inhibitors; D050258:Mitosis Modulators; D009861:Onium Compounds; D050257:Tubulin Modulators; C007517:diphenyleneiodonium