Effect of 5-fluorouracil on cell cycle regulatory proteins in human colon cancer cell line.
We investigated the effects of 5-fluorouracil (5-FU) on cell cycle-regulating proteins in RPMI 4788 cells. 5-FU inhibited cell growth dose-dependently and this growth inhibition was accompanied with cell cycle accumulation in early S phase and increased expression of cyclin A. When cells were released from short-term treatment (3 or 24 h) with 5-FU, the cell cycle started to progress again and cyclin A protein levels decreased. Cyclin A-associated kinase activity assay showed that cyclin A-cyclin-dependent kinase (Cdk) 2 kinase activity was altered by 5-FU treatment concomitantly with the changes in cell cycle state seen in flow cytometric analysis. Furthermore, the elevation of cyclin A protein level by 5-FU treatment was observed in three other human cancer cell lines, DLD-1, H226Br and T.Tn. These results suggest that cyclin A protein levels in cancer cells are increased by 5-FU, and the cyclin A function and degradation mechanism remain normal.
Takeda
H
H
First Department of Surgery, Okayama University Medical School. takeda0@bronze.ocn.ne.jp
Haisa
M
M
Naomoto
Y
Y
Kawashima
R
R
Satomoto
K
K
Yamatuji
T
T
Tanaka
N
N
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D016203:CDC2 Protein Kinase / Q000032:analysis; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects*; D003110:Colonic Neoplasms; D019925:Cyclin A / Q000032:analysis; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D019925:Cyclin A; D011494:Protein Kinases; C102333:histone H1 kinase; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D005472:Fluorouracil