FEBS Letters
Volume 583, Issue 12 , Pages 1859-1866, 18 June 2009

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

Edited by Giulio Superti-Furga

  • Lin Jin

      Affiliations

    • Guangzhoujinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, No.601, West Huangpu Road, Guangzhou 510632 China
    • Institute of Pharmacology Science, Jinan University, Guangzhou 510632, China
    • These authors contributed equally to this manuscript.
    • ,
  • Chuan-Le Xiao

      Affiliations

    • Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China
    • These authors contributed equally to this manuscript.
    • ,
  • Chun-Hua Lu

      Affiliations

    • Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China
    • ,
  • Min Xia

      Affiliations

    • Beijing Guoyaolongli Biomedicine New Technology Co. Ltd., Beijing 102600, China
    • ,
  • Guo-Wen Xing

      Affiliations

    • Chemistry College, Beijing Normal University, Beijing 100875, China
    • ,
  • Sheng Xiong

      Affiliations

    • Guangzhoujinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, No.601, West Huangpu Road, Guangzhou 510632 China
    • ,
  • Qiu-Ying Liu

      Affiliations

    • Guangzhoujinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, No.601, West Huangpu Road, Guangzhou 510632 China
    • ,
  • Hui Liu

      Affiliations

    • Guangzhoujinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, No.601, West Huangpu Road, Guangzhou 510632 China
    • Institute of Pharmacology Science, Jinan University, Guangzhou 510632, China
    • ,
  • Yi-Cheng Li

      Affiliations

    • Guangzhoujinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, No.601, West Huangpu Road, Guangzhou 510632 China
    • ,
  • Feng Ge

      Affiliations

    • Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China
    • ,
  • Qing-Duan Wang

      Affiliations

    • Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou 450052, China
    • ,
  • Qing-Yu He

      Affiliations

    • Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China
    • ,
  • Yi-Fei Wang

      Affiliations

    • Guangzhoujinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, No.601, West Huangpu Road, Guangzhou 510632 China
    • Corresponding Author InformationCorresponding author. Fax: +86 20 85223426.

Received 21 March 2009; received in revised form 17 April 2009; accepted 23 April 2009. published online 08 May 2009.

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.

Structured summary

MINT-7033976: BAD (uniprotkb:Q92934) physically interacts (MI:0218) with Bcl2-Xl (uniprotkb:Q07817) by anti bait coimmunoprecipitation (MI:0006)

Abbreviations: 17-AAG, 17-(allylamino)-17-demethoxygeldanmycin, DMSO, dimethylsulfoxide, CML, chronic myeloid leukemia, FBS, fetal bovine serum, IEF, isoelectric focusing, IPG, immobilized pH gradient, PRDX5, peroxiredoxin V, DLD, dihydrolipoamide dehydrogenase, ECH1, enoyl coenzyme A hydratase 1, IDH3A, isocitrate dehydrogenase alpha subunit, ALDH2, aldehyde dehydrogenase 2 family, NDUFV2, NADH dehydrogenase flavoprotein 2, TRAP1, tumor necrosis factor-associated protein 1, Crkl, v-crk sarcoma virus CT10 oncogene homolog (avian)-like, Grb2, growth factor receptor bound protein 2

Keywords: SNX-2112, K562 cell, Apoptosis, Transcriptomic, Proteomic, Mitochondria dysfunction

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PII: S0014-5793(09)00359-7

doi:10.1016/j.febslet.2009.04.046

FEBS Letters
Volume 583, Issue 12 , Pages 1859-1866, 18 June 2009

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