title: Possible role of HSP60 in synergistic action of anthracyclines and sulindac in HeLa cells.
abstract: As was observed in the earlier studies, doxorubicin (DOX) induced apoptosis in HeLa cells and that effect was potentiated significantly by sulindac (SUL). The aim of the current work was to study the effects of DOX and SUL on HSP60, HSF1 and HSP60 expression and the influence of DOX and SUL on HSP60 translocation. Expression of HSP60 and HSF1 was determined with QRT-PCR; the expression and localization of HSP60 were evaluated with Western blot. The 24-h cell cultures were co-incubated with DOX - 1 microM and/or SUL - 50 microM. The significant induction of HSF1 and HSP60 mRNA level was observed after exposure of the cells to DOX 1 microM. SUL 50 microM alone caused moderate increase in mRNA level. The significant decrease in expression of HSF1 and HSP60 was noted after DOX 1 microM and SUL 50 microM simultaneous treatment. HSP60 appeared in the higher levels in cytosol than in mitochondria No intracellular translocation was noted under treatment of the cells to DOX and/or SUL. In conclusion, the effects of HSP60 and HSF1 evoked in the cells depend on the inducer, proapoptotic action of DOX + SUL may correlate to the increased expression of HSF1 and HSP60; HSP60 mRNA level and the regulation of that protein expression depend on the apoptotic inducer; the role of HSP60 in apoptosis expressed in potential shift between mitochondria and cytosol is determined by the apoptotic inducer and the cell type.
authors.affiliation: Department of Biochemistry and Biopharmaceuticals, National Medicines Institute, Chełmska St. 30/34, 00-725 Warszawa, Poland. b-gruber@il.waw.pl
authors.forename: Beata M
authors.initials: BM
authors.lastname: Gruber
authors.forename: Jolanta
authors.initials: J
authors.lastname: Krzysztoń-Russjan
authors.forename: Irena
authors.initials: I
authors.lastname: Bubko
authors.forename: Elzbieta L
authors.initials: EL
authors.lastname: Anuszewska
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013467:Sulindac / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018834:Chaperonin 60; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; D013467:Sulindac; D004317:Doxorubicin