Potentiation of cytotoxicity of 1-beta-D-arabinofuranosylcytosine for K562 human leukemic cells by cadeguomycin.
The treatment of K562 human myeloblastic leukemia cells and YAC-1 murine lymphoma cells with cadeguomycin at concentrations over 0.6 microM significantly enhanced the cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C). The degree of potentiation depended upon the antibiotic concentration. The treatment with 75 microM cadeguomycin for 18 h increased cellular uptake of [3H]ara-C into K562 cells and formation of ara-C nucleotides, as well as incorporation into nucleic acids. The level of the diphosphate of ara-C plus the triphosphate of ara-C was approximately 10 times higher in the cadeguomycin-treated cells than in the untreated cells by 30 min of incubation with [3H]ara-C. The extracts of 15 microM cadeguomycin-treated K562 cells showed increased activity of formation of ara-C nucleotides, resulting in 4- to 5-fold higher formation of the di- and triphosphates of ara-C than the control cell extracts. Cadeguomycin did not significantly change the level of ribonucleotide and deoxyribonucleotide pool in K562 cells. The mechanism of potentiation of ara-C by cadeguomycin was discussed.
Suzuki
H
H
Kim
S H
SH
Tanara
M
M
Okazaki
K
K
Okabe
T
T
Wu
R T
RT
Tanaka
N
N
D000900:Anti-Bacterial Agents / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000378:metabolism / Q000633:toxicity*; D004357:Drug Synergism; D006151:Guanosine / Q000031:analogs & derivatives / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute; D014316:Tritium
D000900:Anti-Bacterial Agents; D003561:Cytarabine; D014316:Tritium; D006151:Guanosine; C034568:cadeguomycin