Taxnes (taxoids) are a new group of compounds with a significant anticancer
activity. These compounds are mainly used for therapy of breast and ovaria
n cancer. Paditaxel and docetaxel, two representatives of these anticancer
drugs, are natural products extracted from Taxus brevifolia and T. baccam L
., respectively. Taxanes exhibit a unique mechanism of action. They prevent
depolymerization of microtubules, important proteins in cell proliferation
. Taxanes rank among the so-called mitotic poisons: docetaxel is mainly act
ive in the S phase, while paclitaxel in the G(2)/M phase of the cell cycle.
Metabolism of paclitaxel in humans is different from that in experimental
animals. Major human metabolite of paclitaxel is 6 alpha-hydroxypaclitaxel.
Formation of this metabolite is catalyzed by CYP2C8, while the CYP3A subfa
mily mediates formation of minor metabolites of paclitaxel. Docetaxel is me
tabolized in humans and rats in the same way; therefore, rats are a suitabl
e model for studies of docetaxel metabolism in humans. The major metabolite
is hydroxydocetaxel. CYP3As were identified as the enzymes participating i
n metabolism of docetaxel in both species. The review summarizes data conce
rning the mechanism of action of taxanes and their metabolism. Additional i
nformation on metabolic transformalion of these anticancer drugs may serve
for potential improvement of their chemotherapeutic efficiencies.