Alterations in polyamine levels induced by phorbol diesters and other agents that promote differentiation in human promyelocytic leukemia cells

Journal Article · Sun Feb 01 00:00:00 EST 1981 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.78.2.1062· OSTI ID:6357294

Huberman, E; Weeks, C; Herrmann, A; Callaham, M; Slaga, T

Polyamine levels were evaluated in human HL-60 promyelocytic leukemia cells after treatment with inducers of terminal differentiation. Differentiation in these cells was determined by increases in the percentage of morphologically mature cells and in lysozyme activity. Treatment of the HL-60 cells with phorbol 12-myristate-13-acetate (PMA), phorbol 12,13-didecanoate or other inducers of terminal differentiation such as dimethylsulfoxide and retinoic acid resulted in increased levels of putrescine. However, no increase in putrescine could be detected after PMA treatment of a HL-60 cell variant that exhibited a decreased susceptibility to PMA-induced terminal differentiation. Similarly, no increase in putrescine was observed with two nontumor-promoters (phorbol 12,13-diacetate and 4-O-methyl-PMA) or with anthralin, a non-phorbol tumor promoter. In addition to enhancing putrescine levels, PMA also increased the amount of spermidine and decreased the amount of spermine. The increase in putrescine and spermidine preceded the expression of the various differentiation markers. Unlike the changes observed in the polyamine levels after PMA treatment, the activities of ornithine and S-adenosylmethionine decarboxylases, which are polyamine biosynthetic enzymes, did not significantly change. ..cap alpha..-Methylornithine and ..cap alpha..-difluoromethylornithine and methylglyoxal bis(guanylhydrazone), which are inhibitors of the polyamine biosynthetic enzymes, did not affect differentiation in control or PMA-treated cells. Because of these observations, we suggest that the change in polyamine levels involve biochemical pathways other than the known biosynthetic ones. By-products of these pathways may perhaps be the controlling factors involved in the induction of terminal differentiation in the HL-60 and other cell types as well.

• Research Organization: Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
• OSTI ID: 6357294
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 78:2
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
CELL DIFFERENTIATION
GROWTH
TUMOR PROMOTERS
BIOLOGICAL EFFECTS
AMINES
BIOLOGICAL PATHWAYS
CELL CULTURES
DMSO
ESTERS
EXPERIMENTAL DATA
LEUKEMIA
MAN
ORNITHINE
PUTRESCINE
SPERMIDINE
AMINO ACIDS
ANIMALS
CARBOXYLIC ACIDS
DATA
DISEASES
HEMIC DISEASES
INFORMATION
MAMMALS
NEOPLASMS
NUMERICAL DATA
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PRIMATES
PROMOTERS
SULFOXIDES
VERTEBRATES
550200* - Biochemistry
550300 - Cytology