Taxol: mechanisms of action and resistance.
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.
Horwitz
S B
SB
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461.
Cohen
D
D
Rao
S
S
Ringel
I
I
Shen
H J
HJ
Yang
C P
CP
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*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D017239:Paclitaxel