The apoptogenic response of human myeloid leukaemia cell lines and of normal and malignant haematopoietic progenitor cells to the proteasome inhibitor PSI
British Journal of Haematology, ISSN: 0007-1048, Vol: 113, Issue: 1, Page: 126-135
2001
- 90Citations
- 23Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations90
- Citation Indexes90
- 90
- CrossRef64
- Captures23
- Readers23
- 23
Article Description
Degradation of several intracellular proteins involved in cell cycle control and tumour growth is regulated by the ubiquitin-dependent multicatalytic protease complex (proteasome). We report that proteasome inhibitor Z-Ile-Glu(OtBu)-Ala-Leucinal (PSI) was cytotoxic on most human myeloid leukaemia cell lines at IC doses ranging from 5 to 25 nmol/l. Additionally, PSI pretreatment enhanced cytotoxicity by taxol and cisplatinum. PSI was more active on leukaemic than on normal CD34 bone marrow progenitors because the 50% growth inhibition of colony-forming unit granulocyte macrophage (CFU-GM) from cases of chronic myelogenous leukaemia (CML) and normal subjects was achieved by 15 nmol/l and 50 nmol/l PSI respectively. PSI killed cells by apoptosis as revealed by ultrastructural changes, nuclear DNA fragmentation, cleavage of poly (ADP-ribose) polymerase (PARP) and of β-catenin, and was antagonized by ectopic expression of Bcl-2 but not by inactivating mutations of p53. This event was associated with a slight accumulation of Bcl-2, a decrease of Bax but no changes in Bcl-X protein expression at any time point. In Ph cell lines BCR-ABL protein was only down-regulated after 48 h of treatment with 10 nmol/l PSI. Altogether, these results indicate that PSI, alone or in association with other cytotoxic agents, has anti-tumour activity against myeloid malignancies and is more effective on leukaemic than on normal haematopoietic progenitor cells.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0035000515&origin=inward; http://dx.doi.org/10.1046/j.1365-2141.2001.02683.x; http://www.ncbi.nlm.nih.gov/pubmed/11328292; https://onlinelibrary.wiley.com/doi/10.1046/j.1365-2141.2001.02683.x; https://dx.doi.org/10.1046/j.1365-2141.2001.02683.x; https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2141.2001.02683.x
Wiley
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