title: Modulation of heat-shock protein 70 (HSP70) gene expression by sodium butyrate in U-937 promonocytic cells: relationships with differentiation and apoptosis.
abstract: The administration of sodium butyrate at 0.75 mM induced the functional differentiation of U-937 human promonocytic leukemia cells with negligible cell mortality. However, the drug rapidly caused cell death with characteristics of apoptosis when used at concentrations of 5 mM and above. In addition, butyrate stimulated the expression of the stress-responsive heat-shock protein 70 (HSP70) gene when applied at both differentiation-inducing and apoptosis-inducing concentrations. The induction of HSP70 by butyrate was inhibited by the simultaneous addition of cAMP-increasing agents (dibutyryl cAMP or the combination of forskolin plus theophylline). However, these agents did not prevent differentiation and only partially reduced apoptosis. Moreover, the DNA topoisomerase II inhibitor etoposide, which provoked U-937 cell differentiation and apoptosis with the same or greater efficiency than butyrate, failed to stimulate HSP70 expression. Finally, it was observed that cAMP-increasing agents also abrogated the induction of HSP70 and reduced the apoptosis caused by cadmium chloride, a typical inducer of the stress response. Taken together, these results indicate that HSP70 expression is not required for differentiation of promonocytic cells, as earlier proposed, and that butyrate probably triggers the stress response in these cells.
authors.affiliation: Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Garcia-Bermejo
authors.forename: N E
authors.initials: NE
authors.lastname: Vilaboa
authors.forename: C
authors.initials: C
authors.lastname: Perez
authors.forename: A
authors.initials: A
authors.lastname: Galan
authors.forename: E
authors.initials: E
authors.lastname: De Blas
authors.forename: P
authors.initials: P
authors.lastname: Aller
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D019256:Cadmium Chloride / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006633:Histamine Antagonists / Q000494:pharmacology*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002087:Butyrates; D002273:Carcinogens; D018840:HSP70 Heat-Shock Proteins; D006633:Histamine Antagonists; D010726:Phosphodiesterase Inhibitors; D059005:Topoisomerase II Inhibitors; D020148:Butyric Acid; D005576:Colforsin; D003994:Bucladesine; D005047:Etoposide; D013806:Theophylline; D000242:Cyclic AMP; D019256:Cadmium Chloride