Document Detail


Differential impact of bortezomib on HL-60 and K562 cells.
MedLine Citation:
PMID:  25367763     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Bortezomib (PS-341, or Velcade), reversible inhibitor of 20S proteasome approved for the treatment of multiple myeloma and mantle cell lymphoma, exhibited a cytotoxic effect toward other malignancies including leukaemia. In this study, we have documented that incubation of both HL-60 and K562 leukaemia cells with nanomolar concentrations of bortezomib is associated with the death of HL-60 cells observed within 24 hours of incubation with bortezomib and the death of K562 cells that were observed after 72 hours of incubation with bortezomib. The relative resistance of K562 cells to bortezomib correlated well with significantly higher expression of HSP27, HSP70, HSP90α, HSP90β and GRP75 in these cells. Incubation of both HL-60 and K562 cells with bortezomib induced a cleavage of HSP90β as well as expression of HSP70 and HSP90β but bortezomib did not affect levels of HSP27, HSP90α, GRP75 and GRP78. The death of both types of cells was accompanied with proteolytic activation of caspase 3 that was observed in HL-60 cells and proteolytic degradation of procaspase 3 in K562 cells. Our study has also pointed to essential role of caspase 8 in bortezomib-induced cleavage of HSP90β in both HL-60 and K562 cells. Finally, we have shown that bortezomib induced activation of caspase 9/caspase 3 axis in HL-60 cells, while the mechanism of death of K562 cells remains unknown.
Authors:
Katarína Kliková; Andrea Stefaniková; Ivana Pilchová; Jozef Hatok; Peter Chudý; Juraj Chudej; Dušan Dobrota; Peter Račay
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-4
Journal Detail:
Title:  General physiology and biophysics     Volume:  -     ISSN:  0231-5882     ISO Abbreviation:  Gen. Physiol. Biophys.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-4     Completed Date:  -     Revised Date:  2014-11-5    
Medline Journal Info:
Nlm Unique ID:  8400604     Medline TA:  Gen Physiol Biophys     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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