Reduction in lactate accumulation correlates with differentiation-induced terminal cell division of leukemia cells.
Lactate accumulation in the medium and glucose utilization decreased during the induction of in vitro differentiation of mouse erythroleukemia (MEL) and human myeloid leukemia (HL-60) cells. The decrease in lactate accumulation occurred as early as 24 h after inducer treatment was initiated and occurred prior to the decrease in glucose utilization. The decrease in lactate accumulation was greater than that predicted by the decrease in glucose utilization, i.e., the ratio of glucose used glycolytically, as measured by lactate accumulation, to glucose used in other pathways ('glycolytic ratio') markedly decreased during differentiation in these cell lines. Differentiation correlated with the abrogation of the high levels of lactate accumulation first described by Warburg as characteristic of some transformed and neoplastic cells. Studies on both parental and differentiation-resistant variant MEL cell lines indicated that the changes in lactate accumulation were not dependent on the changes in glucose utilization and could be dissociated from them. Moreover, the changes in lactate accumulation only occurred in cells able to undergo differentiation-induced terminal cell division. This regulatable expression of lactate accumulation in MEL and HL-60 cells in vitro may make them useful model systems for the elucidation of the molecular mechanisms controlling lactate formation in malignant cells.
Wu
H
H
Department of Medicine, Rochelle Belfer Chemotherapy Foundation Laboratory, Mount Sinai Medical Center, New York, NY 10029.
Scher
B M
BM
Chu
C L
CL
Leonard
M
M
Olmedo
R
R
Scher
G S
GS
Stecker
S
S
Scher
W
W
Waxman
S
S
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D003907:Dexamethasone / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000473:pathology*; D007951:Leukemia, Myeloid / Q000473:pathology*; D051379:Mice
D000081:Acetamides; D005971:Glutamates; D007773:Lactates; D005973:Glutamine; D002245:Carbon Dioxide; D019344:Lactic Acid; D018698:Glutamic Acid; D003907:Dexamethasone; C014026:hexamethylene bisacetamide; D004121:Dimethyl Sulfoxide