Potentiation of cytotoxicity of 1-beta-D-arabinofuranosylcytosine for K562 human leukemic cells by cadeguomycin.

Abstract

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.

• Authors: H Suzuki, S H Kim, M Tanara, K Okazaki, T Okabe, R T Wu, N Tanaka
• Journal: Cancer research (Cancer Res) Vol. 47 Issue 3 Pg. 713-7 (Feb 01 1987) ISSN: 0008-5472 [Print] United States
• PMID: 3467840 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Cytarabine
• Tritium
• Guanosine
• cadeguomycin

Topics

• Anti-Bacterial Agents (toxicity)
• Cell Division (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Cytarabine (metabolism, toxicity)
• Drug Synergism
• Guanosine (analogs & derivatives, toxicity)
• Humans
• Kinetics
• Leukemia, Myeloid, Acute
• Tritium