In vitro suppression of leukemia by alkylated interleukin-3.
We report the in vitro suppression of the IL-3-dependent MO-7 acute myeloid leukemia proliferation by an interleukin-3 antagonist. The antagonist was generated by alkylation to inactivate catalytic His-residues of native human interleukin-3. The resulting inhibitor caused a factor 7 inhibition of the growth-response curve of the IL-3 control-stimulated proliferation of a MO-7 leukemia cell line. A 40% inhibition of the MO-7 proliferation could be achieved with a partially alkylated inhibitor in presence of a factor 30 excess of native IL-3. Therefore, the inhibitor had a substantially improved affinity for the IL-3 receptor on these leukemia cells. At a concentration of as low as 0.1 ng/ml it still caused a 2-fold inhibition of the native IL-3-stimulated proliferation response curve. Thus it can be concluded that this alkylate IL-3 is a potent IL-3 antagonist. Based on the reported specific zinc binding of IL-2, IL-6, GM-CSF and gamma-interferon this suggests that more leukemias and even other forms of cancer can be effectively suppressed by alkylated growth factors.
Smit
V
V
Trojan Horms Incorporated, Delft, The Netherlands.
D000208:Acute Disease; D000478:Alkylation; D002384:Catalysis; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015032:Zinc / Q000378:metabolism
D007377:Interleukin-3; D007461:Iodoacetates; D014316:Tritium; D015032:Zinc; D013936:Thymidine; D019807:Iodoacetic Acid