Inhibition of amino acid uptake and incorporation into proteins in Friend erythroleukemia cells by the anthracycline antitumor antibiotic aclacinomycin A.
Treatment of Friend erythroleukemia cells with aclacinomycin A caused a concomitant inhibition of the uptake of 14C-alpha-aminoisobutyric acid (AIB) and of the incorporation of 3H-alanine into proteins. The decrease in amino acid uptake and incorporation into proteins was dose-dependent and reached a maximum of 60% within 3 hours at the concentration of aclacinomycin A, 200 ng/ml. A comparison of the effect on protein incorporation of 3H-alanine and cell proliferation by various anthracycline antitumor antibiotics in a concentration range of 50-200 ng/ml revealed that two other N-alkylated anthracyclines, pyrromycin and marcellomycin, are also potent inhibitors of the incorporation of amino acids into proteins. Inhibition of amino acid incorporation into proteins correlated well with the reduction of cell number at a later time. In contrast, adriamycin and daunomycin inhibited the incorporation of 3H-alanine into proteins only weakly, although these substances were highly active at inhibiting cell proliferation. Studies with an inhibitor of RNA synthesis, actinomycin D, suggest that the concomitant inhibition of amino acid uptake and incorporation into proteins observed with aclacinomycin A is not due to a reduced RNA synthesis. In addition, aclacinomycin A, up to a concentration of 10 micrograms/ml, did not inhibit protein synthesis in a cell-free translational system from rabbit reticulocytes. These results indicate that the reduction of amino acid incorporation into proteins after treatment of Friend erythroleukemia cells with aclacinomycin A may be due to a reduced uptake of amino acids. Inhibition of the transport of 14C-AIB may be indicative for an interaction of aclacinomycin A with the plasma membrane.
Schaefer
A
A
Department of Toxicology, Hamburg University Medical School, Federal Republic of Germany.
Boldt
J
J
Westendorf
J
J
Steinheider
G
G
Marquardt
H
H
D015250:Aclarubicin; D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005622:Friend murine leukemia virus; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D009279:Naphthacenes / Q000494:pharmacology; D014176:Protein Biosynthesis; D011817:Rabbits; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D003609:Dactinomycin; C100049:2-aminoisobutyric acid; D015250:Aclarubicin; D000409:Alanine