Potentiation of the bleomycin, arabinofuranosylcytosine and adriamycin-caused inhibition of DNA synthesis in lymphocytes by bestatin in vitro.
Combinations of 1-beta-D-arabinofuranosylcytosine (araC), bleomycin (BLM) or adriamycin (ADM) with the dipeptide bestatin do not result in an enhanced in vitro cytotoxicity in the macrophage-free L5178y mouse lymphoma cell system. However, in macrophage-containing murine spleen lymphocytes bestatin causes a potentiating effect of the cytostatic drugs araC, BLM and ADM with respect to their potencies to inhibit DNA synthesis. In the presence of 1 microgram bestatin/ml, the ED50 concentrations causing a 50% reduction of [3H]dThd incorporation were significantly lowered; 4.3-fold in the studies with araC and BLM, and 1.8-fold in the experiments with ADM. Bestatin, given alone, displays a stimulating effect on [3H]dThd incorporation into macrophage-containing lymphocyte cultures within the concentration range 0.1-10 micrograms/ml. In contrast to the bestatin-stimulated lymphocytes, ConA-stimulated as well as LPS-stimulated lymphocytes do not show a higher sensitivity to the selected drugs inhibiting DNA synthesis. These data should encourage the practical use of bestatin in combination with araC, BLM or ADM in cancer treatment.
G
G
Leyhausen
H C
HC
Schröder
D K
DK
Schuster
A
A
Maidhof
H
H
Umezawa
W E
WE
Müller
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D013936:Thymidine / Q000378:metabolism
D003561:Cytarabine; D001761:Bleomycin; D004317:Doxorubicin; D004247:DNA; D007930:Leucine; C012211:ubenimex; D013936:Thymidine