Prostaglandins with antiproliferative activity induce the synthesis of a heat shock protein in human cells.
Prostaglandins (PGs) A1 and J2 were found to potently suppress the proliferation of human K562 erythroleukemia cells and to induce the synthesis of a 74-kDa protein (p74) that was identified as a heat shock protein related to the major 70-kDa heat shock protein group. p74 synthesis was stimulated at doses of PGA1 and PGJ2 that inhibited cell replication, and its accumulation ceased upon removal of the PG-induced proliferation block. PGs that did not affect K562 cell replication did not induce p74 synthesis. p74 was found to be localized mainly in the cytoplasm of PG-treated cells, but moderate amounts were found also in dense areas of the nucleus after PGJ2 treatment. p74 synthesis was not necessarily associated with cytotoxicity or with inhibition of cell protein synthesis. The results described support the hypothesis that synthesis of the 70-kDa heat shock proteins is associated with changes in cell proliferation. The observation that PGs can induce the synthesis of heat shock proteins expands our understanding of the mechanism of action of these compounds whose regulatory role is well known in many physiological phenomena, including the control of fever production.
Santoro
M G
MG
Institute of Experimental Medicine, Consiglio Nazionale delle Ricerche, Rome, Italy.
Garaci
E
E
Amici
C
C
D002460:Cell Line; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D006801:Humans; D015151:Immunoblotting; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008715:Methionine / Q000378:metabolism; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D011453:Prostaglandins / Q000494:pharmacology*; D011454:Prostaglandins A / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D011453:Prostaglandins; D011454:Prostaglandins A; D008715:Methionine; C100573:prostaglandin A1