POTENTIATION OF CYTOTOXICITY OF 1-BETA-D-ARABINOFURANOSYLCYTOSINE FOR K562 HUMAN-LEUKEMIC CELLS BY CADEGUOMYCIN

  • 1 February 1987
    • journal article
    • research article
    • Vol. 47  (3) , 713-717
Abstract
The treatment of K562 human myeloblastic leukemia cells and YAC-1 murine lymphoma cells with cadeguomycin at concentrations over 0.6 .mu.M significantly enhanced the cytotoxicity of 1-.beta.-D-arabinofuranosylcytosine (ara-C). The degree of potentiation depended upon the antibiotic concentration. The treatment with 75 .mu.M 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 .mu.M cadeguomycin-treated K562 cells showed increased activity of formation of ara-C nucleotides, resulting in 4- to 5-hold 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.