Inhibition of cultured leukemia cell growth by enhanced adriamycin cytotoxicity with reduction of glutamine or asparagine level in medium.
The effect of a singular amino acid, asparagine (Asn), glutamine (Gln), or proline deletion in a cultured medium (RPMI 1640 supplemented with 10% fetal calf serum and other ingredients) on adriamycin (ADR) cytotoxicity was evaluated in the growth of P388 murine leukemia cells and CEM human acute lymphoblastic leukemia cells over a 3 day period. No enhancement of ADR cytotoxicity was observed in the assay of IC50 values under the amino acid deleted condition. Singular deletion of Gln or Asn from ADR-free medium apparently inhibited the proliferation of both cells, i.e. both cell lines strongly require them. The cytotoxicity of 5 nM ADR was then examined in medium which included one or the other of them in stepwise levels varied at 80, 60, 40, 20 and 0% of the ordinary level. Change of Asn level caused a difference in ADR toxicity; also, the change of Gln level, especially the 60% level caused ADR toxicity of 5 nM, which is less than the IC50 value, in the proliferation of both cells. This suggested the usefulness of glutamine level modification on the enhancement of ADR cytotoxicity.
Sukemori
S
S
Rokkou Bio-Scientific Research Laboratory Co., Ltd., Saitama.
Sugimura
K
K
D000818:Animals; D001216:Asparagine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology*; D006801:Humans; D007941:Leukemia P388 / Q000473:pathology*; D051379:Mice; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D011392:Proline / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003470:Culture Media; D005973:Glutamine; D001216:Asparagine; D004317:Doxorubicin; D011392:Proline