Cytochrome P450 CYP1B1 protein expression: a novel mechanism of anticancer drug resistance

Biochem Pharmacol. 2001 Jul 15;62(2):207-12. doi: 10.1016/s0006-2952(01)00643-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Aryl Hydrocarbon Hydroxylases*
  • CHO Cells
  • Cell Survival / drug effects
  • Cricetinae
  • Cytochrome P-450 CYP1B1
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Docetaxel
  • Drug Resistance, Neoplasm / physiology*
  • Humans
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / metabolism
  • Paclitaxel / pharmacology
  • Taxoids*
  • Transfection


  • Antineoplastic Agents
  • Taxoids
  • Docetaxel
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1B1
  • Paclitaxel