Effects of the combination of acivicin and cis-diamminedichloroplatinum(II) on thymidylate synthesis of A549 lung cancer cells.
Compared to either compound alone, the combination of acivicin and cis-diamminedichloroplatinum(II) markedly enhanced the inhibition of the activities of thymidylate synthase and thymidine kinase, the enzymes involved in the final steps of the de novo and salvage pathways in pyrimidine metabolism in A549 lung cancer cells. The enhancement of enzymic inhibition paralleled that of cell growth inhibition. These results indicate that the combination of these drugs can inhibit the capacities of the pyrimidine pathways, resulting in an efficient reduction of DNA synthesis.
Futami
H
H
First Department of Internal Medicine, Kagawa Medical School, Japan.
Shiotani
T
T
Yamaji
Y
Y
Yamauchi
N
N
Irino
S
S
D000963:Antimetabolites / Q000494:pharmacology*; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology*; D004338:Drug Combinations; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010080:Oxazoles / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors; D013938:Thymidine Monophosphate / Q000096:biosynthesis*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D013942:Thymine Nucleotides / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
D000963:Antimetabolites; D004338:Drug Combinations; D006131:Growth Inhibitors; D007555:Isoxazoles; D010080:Oxazoles; D013942:Thymine Nucleotides; D013938:Thymidine Monophosphate; D013940:Thymidylate Synthase; D013937:Thymidine Kinase; C006303:acivicin; D002945:Cisplatin