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Celastrol, a novel HSP90 inhibitor, depletes Bcr-Abl and induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation.
- Source :
-
Cancer letters [Cancer Lett] 2010 Apr 28; Vol. 290 (2), pp. 182-91. Date of Electronic Publication: 2009 Oct 12. - Publication Year :
- 2010
-
Abstract
- T315I Bcr-Abl in chronic myelogenous leukemia (CML) is the most notorious point mutations to elicit acquired resistance to imatinib. In the present study, we investigated the effect of celastrol on CML cells bearing wild-type Bcr-Abl or T315I-mutant. The results revealed that celastrol potently downregulated the protein levels of Bcr-Abl, and inhibited the growth in CML cells in vitro and in nude mouse xenografts regardless of Bcr-Abl mutation status. Celastrol induced mitochondrial-dependent apoptosis. In conclusion, celastrol exhibits potent activity against CML cells bearing wild-type Bcr-Abl or -the T315I-mutant.<br /> (2009 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Benzamides
Blotting, Western
Cell Line, Tumor
Cell Separation
Drug Resistance, Neoplasm drug effects
Electrophoresis, Polyacrylamide Gel
Flow Cytometry
HSP90 Heat-Shock Proteins antagonists & inhibitors
Humans
Imatinib Mesylate
Immunohistochemistry
Male
Mice
Mice, Nude
Mutation
Neoplasms, Experimental drug therapy
Neoplasms, Experimental metabolism
Pentacyclic Triterpenes
Piperazines pharmacology
Pyrimidines pharmacology
Signal Transduction drug effects
Xenograft Model Antitumor Assays
Antineoplastic Agents pharmacology
Apoptosis drug effects
Fusion Proteins, bcr-abl drug effects
Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Triterpenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 290
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 19819619
- Full Text :
- https://doi.org/10.1016/j.canlet.2009.09.006