Cytochrome P450 CYP1B1 protein expression: a novel mechanism of anticancer drug resistance.
Biochem Pharmacol
; 62(2): 207-12, 2001 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-11389879
ABSTRACT
The overexpression of human cytochrome P450 CYP1B1 has been observed in a wide variety of malignant tumours, but the protein is undetectable in normal tissues. A number of cytochrome P450 enzymes are known to metabolise a variety of anticancer drugs, and the consequence of cytochrome P450 metabolism is usually detoxification of the drug, although bioactivation occurs in some cases. In this study, a Chinese hamster ovary cell line expressing human cytochrome P450 CYP1B1 was used to evaluate the cytotoxic profile of several anticancer drugs (docetaxel, paclitaxel, cyclophosphamide, doxorubicin, 5-fluorouracil, cisplatin, and carboplatin) commonly used clinically in the treatment of cancer. The MTT (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide) assay was used to determine the levels of cytotoxicity. The key finding of this study was that on exposure to docetaxel, a significant decrease in sensitivity towards the cytotoxic effects of docetaxel was observed in the cell line expressing CYP1B1 compared to the parental cell line (P = 0.03). Moreover, this difference in cytotoxicity was reversed by co-incubation of the cells with both docetaxel and the cytochrome P450 CYP1 inhibitor alpha-naphthoflavone. This study is the first to indicate that the presence of CYP1B1 in cells decreases their sensitivity to the cytotoxic effects of a specific anticancer drug.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hidrocarboneto de Aril Hidroxilases
/
Paclitaxel
/
Resistencia a Medicamentos Antineoplásicos
/
Sistema Enzimático do Citocromo P-450
/
Taxoides
/
Antineoplásicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Reino Unido