Microtubule disruptors and their interaction with biotransformation enzymes.
Microtubule disruptors, widely known as antimitotics, have broad applications in human medicine, especially as anti-neoplastic agents. They are subject to biotransformation within human body frequently involving cytochromes P450. Therefore antimitotics are potential culprits of drug-drug interactions on the level of activity as well as expression of cytochromes P450. This review discusses the effects of four well-known natural antimitotics: colchicine, taxol (paclitaxel), vincristine, and vinblastine, and a synthetic microtubule disruptor nocodazole on transcriptional activity of glucocorticoid and aryl hydrocarbon receptors. It appears that microtubules disarray restricts the signaling by these two nuclear receptors regardless of cell cycle phase. Consequently, intact microtubules play an important role in the regulation of expression of cytochromes P450, which are under direct or indirect control of the two nuclear receptors.
Modrianský
Martin
M
Institute of Medical Chemistry and Biochemistry, Palacký University, Hnevotínská 3, Olomouc, 775 15 Czech Republic.
Dvorák
Zdenĕk
Z
D050256:Antimitotic Agents / Q000494:pharmacology*; D001711:Biotransformation; D003078:Colchicine / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015398:Signal Transduction; D014747:Vinblastine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D050256:Antimitotic Agents; D018336:Receptors, Aryl Hydrocarbon; D011965:Receptors, Glucocorticoid; D014750:Vincristine; D014747:Vinblastine; D003577:Cytochrome P-450 Enzyme System; D017239:Paclitaxel; D015739:Nocodazole; D003078:Colchicine