Transcriptomic and proteomic approach to studying SNX-2112-induced K562 cells apoptosis and anti-leukemia activity in K562-NOD/SCID mice.
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.
Mesh Terms:
Animals, Antineoplastic Agents, Apoptosis, Gene Expression Profiling, HSP90 Heat-Shock Proteins, Heterocyclic Compounds with 4 or More Rings, Humans, K562 Cells, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Membrane Potential, Mitochondrial, Mice, Mice, Inbred NOD, Mice, SCID, Mitochondria, Mitochondrial Proteins, Neoplasm Proteins, Neoplasm Transplantation, Proteomics, Signal Transduction, Transplantation, Heterologous, bcl-Associated Death Protein, bcl-X Protein
Animals, Antineoplastic Agents, Apoptosis, Gene Expression Profiling, HSP90 Heat-Shock Proteins, Heterocyclic Compounds with 4 or More Rings, Humans, K562 Cells, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Membrane Potential, Mitochondrial, Mice, Mice, Inbred NOD, Mice, SCID, Mitochondria, Mitochondrial Proteins, Neoplasm Proteins, Neoplasm Transplantation, Proteomics, Signal Transduction, Transplantation, Heterologous, bcl-Associated Death Protein, bcl-X Protein
FEBS Lett.
Date: Jun. 18, 2009
PubMed ID: 19427857
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