title: Taxol: mechanisms of action and resistance.
abstract: Information on the mechanisms of action and of resistance to Taxol, as well as new data from our laboratory on the promoter regions of the genes that encode P-glycoprotein in a murine Taxol-resistant cell line, is discussed. Taxol induces the formation of stable bundles of microtubules, thereby interfering with the normal function of cellular microtubules. The drug can induce the multidrug-resistance (MDR) phenotype that includes the overproduction of P-glycoprotein, a membrane glycoprotein that acts as a drug efflux pump. In human tumors resistant to Taxol, P-glycoprotein could be responsible for maintaining the drug below cytotoxic levels. Analyses of the MDR promoters that are involved in P-glycoprotein expression and overproduction revealed an interesting recombination event in a Taxol-resistant cell line. As an important new clinical agent for the treatment of malignancies, Taxol requires further mechanistic investigations at the preclinical level.
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461.
authors.forename: S B
authors.initials: SB
authors.lastname: Horwitz
authors.forename: D
authors.initials: D
authors.lastname: Cohen
authors.forename: S
authors.initials: S
authors.lastname: Rao
authors.forename: I
authors.initials: I
authors.lastname: Ringel
authors.forename: H J
authors.initials: HJ
authors.lastname: Shen
authors.forename: C P
authors.initials: CP
authors.lastname: Yang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D017239:Paclitaxel