Microtubule disruptors and their interaction with biotransformation enzymes
Language English Country Czech Republic Media print
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
16601758
Knihovny.cz E-resources
- MeSH
- Antimitotic Agents pharmacology MeSH
- Biotransformation MeSH
- Colchicine pharmacology MeSH
- Drug Interactions MeSH
- Humans MeSH
- Microtubules drug effects MeSH
- Nocodazole pharmacology MeSH
- Paclitaxel pharmacology MeSH
- Receptors, Aryl Hydrocarbon metabolism MeSH
- Receptors, Glucocorticoid metabolism MeSH
- Signal Transduction MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Vinblastine pharmacology MeSH
- Vincristine pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Antimitotic Agents MeSH
- Colchicine MeSH
- Nocodazole MeSH
- Paclitaxel MeSH
- Receptors, Aryl Hydrocarbon MeSH
- Receptors, Glucocorticoid MeSH
- Cytochrome P-450 Enzyme System MeSH
- Vinblastine MeSH
- Vincristine MeSH
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.