Transcriptomic and proteomic approach to studying SNX-2112-induced K562 cells apoptosis and anti-leukemia activity in K562-NOD/SCID mice.

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.
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)
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
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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