Effects of hexamethylene bisacetamide on induction of monocytic differentiation of human U-937 myeloid leukemia cells.
The present studies have examined the effects of hexamethylene bisacetamide (HMBA) on the human U-937 monocytic cell line. HMBA treatment was associated with: (1) decreases in U-937 cell proliferation, (2) increases in nonspecific esterase activity and cell surface antigen expression consistent with monocytic differentiation, (3) decreases in c-myc gene expression, and (4) induction of tumor necrosis factor (TNF) transcripts. Treatment of U-937 cells with HMBA was also associated with increases in phospholipase A2 activity and increases in the release of arachidonic acid and its metabolites. Dexamethasone, an agent previously shown to inhibit monocytic differentiation, had no detectable effect on the down-regulation of c-myc, but blocked the induction of TNF expression. Taken together, the results demonstrate that HMBA induces monocytic differentiation of U-937 cells and that this effect is sensitive, in part, to dexamethasone.
Bernstein
S H
SH
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Boston, MA 02115.
Sherman
M L
ML
Hass
R
R
Nakamura
T
T
Kharbanda
S
S
Kufe
D W
DW
D000081:Acetamides / Q000494:pharmacology*; D000954:Antigens, Surface / Q000032:analysis; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D016259:Genes, myc; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology*; D009000:Monocytes / Q000187:drug effects; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D012334:RNA, Neoplasm / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha
D000081:Acetamides; D000954:Antigens, Surface; D001095:Arachidonic Acids; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D003907:Dexamethasone; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D010741:Phospholipases A; D054467:Phospholipases A2; C014026:hexamethylene bisacetamide