Data from The Histone Deacetylase Inhibitor MGCD0103 Induces Apoptosis in B-Cell Chronic Lymphocytic Leukemia Cells through a Mitochondria-Mediated Caspase Activation Cascade Article Swipe
Victoria El‐Khoury
,
Etienne Moussay
,
Bassam Janji
,
Valérie Palissot
,
Nasséra Aouali
,
Nicolaas H. C. Brons
,
Kris Van Moer
,
Sandrine Pierson
,
Eric Van Dyck
,
Guy Berchem
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1535-7163.c.6532230
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1535-7163.c.6532230
Clinical trials have shown activity of the isotype-selective histone deacetylase (HDAC) inhibitor MGCD0103 in different hematologic malignancies. There are data to support the use of HDAC inhibitors in association with other cancer therapies. To propose a rational combination therapy, it is necessary to depict the molecular basis behind the cytotoxic effect of MGCD0103. In this study, we found that MGCD0103 was substantially more toxic in neoplastic B cells relative to normal cells, and we described the death pathways activated by MGCD0103 in B-cell chronic lymphocytic leukemia (CLL) cells from 32 patients. MGCD0103 decreased the expression of Mcl-1 and induced translocation of Bax to the mitochondria, mitochondrial depolarization, and release of cytochrome c in the cytosol. Caspase processing in the presence of the caspase inhibitor Q-VD-OPh and time course experiments showed that caspase-9 was the apical caspase. Thus, MGCD0103 induced the intrinsic pathway of apoptosis in CLL cells. Moreover, MGCD0103 treatment resulted in the activation of a caspase cascade downstream of caspase-9, caspase-dependent amplification of mitochondrial depolarization, activation of calpain, and Bax cleavage. We propose a model whereby the intrinsic pathway of apoptosis triggered by MGCD0103 in CLL is associated with a mitochondrial death amplification loop. Mol Cancer Ther; 9(5); 1349–60. ©2010 AACR.
Related Topics
Concepts
Apoptosis
Cytochrome c
Cancer research
Chronic lymphocytic leukemia
Mitochondrion
Caspase
Programmed cell death
Intrinsic apoptosis
Histone deacetylase inhibitor
Molecular biology
Histone deacetylase
Cancer cell
Caspase 3
Biology
Leukemia
Chemistry
Histone
Cell biology
Cancer
Biochemistry
Immunology
Genetics
Gene
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1158/1535-7163.c.6532230
- OA Status
- gold
- References
- 47
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4361813103
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4361813103Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1158/1535-7163.c.6532230Digital Object Identifier
- Title
-
Data from The Histone Deacetylase Inhibitor MGCD0103 Induces Apoptosis in B-Cell Chronic Lymphocytic Leukemia Cells through a Mitochondria-Mediated Caspase Activation CascadeWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-03-31Full publication date if available
- Authors
-
Victoria El‐Khoury, Etienne Moussay, Bassam Janji, Valérie Palissot, Nasséra Aouali, Nicolaas H. C. Brons, Kris Van Moer, Sandrine Pierson, Eric Van Dyck, Guy BerchemList of authors in order
- Landing page
-
https://doi.org/10.1158/1535-7163.c.6532230Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1158/1535-7163.c.6532230Direct OA link when available
- Concepts
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Apoptosis, Cytochrome c, Cancer research, Chronic lymphocytic leukemia, Mitochondrion, Caspase, Programmed cell death, Intrinsic apoptosis, Histone deacetylase inhibitor, Molecular biology, Histone deacetylase, Cancer cell, Caspase 3, Biology, Leukemia, Chemistry, Histone, Cell biology, Cancer, Biochemistry, Immunology, Genetics, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
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47Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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