Back to Search
Start Over
The proteasome inhibitor bortezomib interacts synergistically with the histone deacetylase inhibitor suberoylanilide hydroxamic acid to induce T-leukemia/lymphoma cells apoptosis.
- Source :
-
Leukemia (08876924) . Aug2009, Vol. 23 Issue 8, p1507-1514. 8p. 4 Graphs. - Publication Year :
- 2009
-
Abstract
- Interactions between inhibitors of the proteasome and histone deacetylases have been examined in human T-leukemia/lymphoma cells both in vitro and in vivo. Co-exposure of cells to bortezomib and suberoylanilide hydroxamic acid (SAHA) synergistically induces T-leukemia/lymphoma cells to undergo apoptosis, consistent with a significant increase in mitochondrial injury and caspase activation. These events are accompanied by inhibition of cyto-protective signaling pathways, including the nuclear factor (NF)-κB, Raf-1/mitogen-induced extracellular kinase (MEK)/extracellular signal-related kinase (ERK) and AKT pathways, and activation of stress-related cascades, including the stress-activated kinases c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK). Moreover, bortezomib in conjunction with SAHA efficiently induces apoptosis of primary T-leukemia/lymphoma cells and inhibits tumor growth in a murine xenograft model established with subcutaneous injection of Jurkat cells. Taken together, these findings confirm the synergistic anti-tumor effect of the proteasome and histone deacetylase inhibitors, and provide an insight into the future clinical applications of bortezomib–SAHA combining regimen in treating T-cell malignancies.Leukemia (2009) 23, 1507–1514; doi:10.1038/leu.2009.41; published online 12 March 2009 [ABSTRACT FROM AUTHOR]
- Subjects :
- *APOPTOSIS
*MITOCHONDRIA
*PROTEIN kinases
*LYMPHOMAS
*LEUKEMIA
Subjects
Details
- Language :
- English
- ISSN :
- 08876924
- Volume :
- 23
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Leukemia (08876924)
- Publication Type :
- Academic Journal
- Accession number :
- 43639966
- Full Text :
- https://doi.org/10.1038/leu.2009.41