Open AccessExpression of CYP2A6 in Tumor Cells Augments Cellular Sensitivity to Tegafur
Author(s) -
Murayama Norie,
Sai Kimie,
Nakajima Yukiko,
Kaniwa Naoko,
Ozawa Shogo,
Ohno Yasuo,
Sawada Junichi
Publication year - 2001
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2001.tb01125.x
Subject(s) - tegafur , transfection , null cell , cell culture , cyp2a6 , cell growth , prodrug , microbiology and biotechnology , chemistry , biology , cancer research , biochemistry , cancer , enzyme , cytochrome p450 , genetics , cyp1a2
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 μ M. 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.