Etoposide inhibition of methylaminoisobutyric acid transport and its recovery in K562 cells.
Sodium-dependent amino acid transport of methylaminoisobutyric acid (MeAIB) in a human myelogenous leukemic cell line K562 was inhibited by 30 nM etoposide (VP-16). Cell growth in suspension was almost completely suppressed by 30 nM VP-16 after 72 h. Colony formation by K562 cells markedly decreased after 24 h in a culture medium containing 30 nM VP-16, whereas MeAIB transport was inhibited after 72 h. K562 cell proliferation was restored in drug-free medium after recovery from 72-h culture with 30 nM VP-16. Colony formation and MeAIB transport were restored to pretreatment levels after 1-2 weeks. Thus, two conclusions may be drawn. (1) MeAIB transport may be correlated with cellular growth and (2) the effects of VP-16 on MeAIB transport were partially reversible.
Shionoya
S
S
Department of Internal Medicine, School of Medicine, Kitasato University, Kanagawa, Japan.
D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003864:Depression, Chemical; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000473:pathology; D012964:Sodium / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014410:Tumor Stem Cell Assay
D000621:Aminoisobutyric Acids; C017911:2-(methylamino)isobutyric acid; D005047:Etoposide; D003513:Cycloheximide; D012964:Sodium