Expression of CYP2A6 in tumor cells augments cellular sensitivity to tegafur

Jpn J Cancer Res. 2001 May;92(5):524-8. doi: 10.1111/j.1349-7006.2001.tb01125.x.


To examine the role of cytochrome P450 2A6 (CYP2A6) in the cellular sensitivity to an anti-tumor prodrug, tegafur (FT), a CYP2A6 cDNA construct was transfected into cells of a colon cancer cell line, DLD-1. CYP2A6-expressing cells (DLD-1 / CYP2A6 cells) more efficiently catalyzed the conversion of FT to 5-fluorouracil (5-FU) (2.6-fold) and the 7-hydroxylation of coumarin (7.9-fold) than cells transfected with a null construct (DLD-1 / null cells). These results indicated that the expressed CYP2A6 was functionally active. The extent of growth inhibition of the DLD-1 / CYP2A6 cells by FT was greater than that of DLD-1 / null cells; the difference between the DLD-1 / CYP2A6 and DLD-1 / null cells was statistically significant at the concentrations of 250, 500 and 1000 mM. 5-FU, an active metabolite of FT, inhibited the growth of both types of cells to the same extent. Thus, intracellular expression of CYP2A6 can sensitize cells to FT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Aryl Hydrocarbon Hydroxylases*
  • Cell Division / drug effects
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / pathology
  • Coumarins / metabolism
  • Cytochrome P-450 CYP2A6
  • Cytochrome P-450 Enzyme System / genetics*
  • Fluorouracil / metabolism
  • Gene Expression*
  • Humans
  • Hydroxylation
  • Microsomes / metabolism
  • Mixed Function Oxygenases / genetics*
  • Tegafur / metabolism
  • Tegafur / pharmacology
  • Tegafur / therapeutic use*
  • Transfection
  • Tumor Cells, Cultured


  • Antimetabolites, Antineoplastic
  • Coumarins
  • Tegafur
  • Cytochrome P-450 Enzyme System
  • coumarin
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2A6 protein, human
  • Cytochrome P-450 CYP2A6
  • Fluorouracil