Abstract |
SNX-2112, a novel inhibitor of Hsp90 currently used as an anti- tumor drug, induces apoptosis in multiple tumor cell lines. It destabilizes specific client proteins, but the molecular mechanism of the apoptosis effect of SNX-2112 is poorly understood. Here, we analyzed the apoptotic effect of SNX-2112 on human chronic myeloid leukemia (CML) K562 cells. Transcriptomic and proteomic approaches further revealed that caspase signals originated from mitochondria dysfunction, mediated by Akt signaling pathway inactivity. Additionally, SNX-2112 prolonged the survival time of NOD/SCID mice inoculated with K562 tumor cells. Our results demonstrated the therapeutic potential of SNX-2112 against human CML.
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Authors | Lin Jin, Chuan-Le Xiao, Chun-Hua Lu, Min Xia, Guo-Wen Xing, Sheng Xiong, Qiu-Ying Liu, Hui Liu, Yi-Cheng Li, Feng Ge, Qing-Duan Wang, Qing-Yu He, Yi-Fei Wang |
Journal | FEBS letters
(FEBS Lett)
Vol. 583
Issue 12
Pg. 1859-66
(Jun 18 2009)
ISSN: 1873-3468 [Electronic] England |
PMID | 19427857
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- BAD protein, human
- BCL2L1 protein, human
- HSP90 Heat-Shock Proteins
- Heterocyclic Compounds, 4 or More Rings
- Mitochondrial Proteins
- Neoplasm Proteins
- SNX 2112
- bcl-Associated Death Protein
- bcl-X Protein
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects, genetics, physiology)
- Gene Expression Profiling
- HSP90 Heat-Shock Proteins
(antagonists & inhibitors)
- Heterocyclic Compounds, 4 or More Rings
(pharmacology)
- Humans
- K562 Cells
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
(drug therapy, genetics, metabolism)
- Membrane Potential, Mitochondrial
(drug effects)
- Mice
- Mice, Inbred NOD
- Mice, SCID
- Mitochondria
(drug effects, metabolism)
- Mitochondrial Proteins
(genetics, metabolism)
- Neoplasm Proteins
(genetics, metabolism)
- Neoplasm Transplantation
- Proteomics
- Signal Transduction
(drug effects)
- Transplantation, Heterologous
- bcl-Associated Death Protein
(metabolism)
- bcl-X Protein
(metabolism)
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