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Reduction of heat‐shock protein‐70 after prolonged treatment with retinoids: Biological and clinical implications
Author(s) -
Tosi Patrizia,
Visani Giuseppe,
Ottaviani Emanuela,
Gibellini Davide,
Pellacani Annalisa,
Tura Sante
Publication year - 1997
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/(sici)1096-8652(199711)56:3<143::aid-ajh2>3.0.co;2-y
Subject(s) - propidium iodide , retinoic acid , heat shock protein , western blot , tretinoin , retinoid , apoptosis , heat shock , microbiology and biotechnology , biology , hsp70 , blot , chemistry , biochemistry , programmed cell death , gene
Heat shock proteins (HSPs) are a group of highly conserved polypeptides involved in cellular response to heat or other physical or chemical stresses. It has been recently reported that HSPs could play a role in cellular differentiation. In this study we have evaluated, by a cytofluorimetric method, the presence of HSP‐70 in HL‐60 cells during treatment with all‐trans retinoic acid (ATRA), 9‐cis retinoic acid (9‐cis RA), and 13‐cis retinoic acid (13‐cis RA). After 1 and 3 days of incubation at 10 −7 M, HSP‐70 did not show any variation compared to control; prolonging the exposure, together with the appearance of cellular differentiation along the granulocytic pathway and apoptosis, a progressive decrease of HSP‐70 was observed that, after 8 days of treatment, was reduced by 40% with ATRA and by 28% with 9‐cis RA compared to untreated samples, while only minimal changes were evident by incubating the cells with 13‐cis RA. Reduction of HSP‐70 was not associated with decreased protein synthesis, as demonstrated by [ 3 H] leucine incorporation. Double labeling with propidium iodide showed a decrease in HSP‐70 in all the phases of the cell cycle concomitant with a reduced percentage of cycling cells in ATRA‐treated samples. Dot blot and Northern blot analysis demonstrated no change in HSP‐70 mRNA after retinoid treatment, thus suggesting a post‐transcriptional regulation of the phenomenon. This reduced production of HSP‐70 caused by ATRA and by 9‐cis RA, though to a lesser extent, could render the cells more sensitive to cytotoxic agents and could provide the rationale for the efficacy of ATRA + chemotherapy combinations. Am. J. Hematol. 56:143–150, 1997. © 1997 Wiley‐Liss, Inc.