The preferential induction of apoptosis in multidrug-resistant KB cells by 5-fluorouracil.
It has been previously been shown that multidrug resistance may be associated with biochemical changes which increase the sensitivity of resistant cells to the induction of apoptosis by certain agents. We have shown here that 48 h exposure to 5-fluorouracil (5-FU) induces both a significantly greater proportion of apoptotic cells and much greater cleavage of the apoptosis-related protein poly-(ADP-ribose)-polymerase in the multidrug-resistant (MDR) carcinoma cell line, KB-A1, than in corresponding drug-sensitive control KB-3.1 cells. Exposure to 5-FU also reduced the level of the anti-apoptotic protein, protein kinase B, in the MDR cells, but not in the control cells.
Warr
J R
JR
Department of Biology, University of York, P.O. Box 373, YO10 5YW, York, UK. jrw6@york.ac.uk
Bamford
A
A
Quinn
D M
DM
D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D005472:Fluorouracil / Q000633:toxicity*; D006801:Humans; D007624:KB Cells; D007700:Kinetics; D009336:Necrosis; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt
D011518:Proto-Oncogene Proteins; D011065:Poly(ADP-ribose) Polymerases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005472:Fluorouracil