Literature DB >> 22494070

Na+/H+ exchanger 1 inhibition contributes to K562 leukaemic cell differentiation.

Weina Jin1, Qinghua Li, Jian Wang, Guoqiang Chang, Yani Lin, Huawen Li, Lihong Wang, Wei Gao, Tianxiang Pang.   

Abstract

The effect of hypoxia on the differentiation of chronic myeloid leukaemic K562 cells were studied, as was the role of the NHE1 (Na+/H+ exchanger 1). Hypoxia induced differentiation of K562 cells as seen by modifications in their morphological features, up-regulation of C/EBPα (CCAAT/enhancer-binding protein α), and marked IL-8 (interleukin-8) release. Inhibition of NHE1 under hypoxia additionally enhanced the level of C/EBPα and further promoted leukaemic cells differentiation. Pharmacological inhibition of p38 MAPK (mitogen-activated protein kinase) also significantly suppressed C/EBPα expression under hypoxia conditions after NHE1 inhibition. These results indicate the enhancement of hypoxia-induced K562 differentiation by NHE1 inhibition, which may be due to up-regulation of C/EBPα via p38 MAPK signalling pathway, which suggests a possible therapeutic target of NHE1 under hypoxia microenvironment in the treatment of leukaemic diseases.

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Year:  2012        PMID: 22494070     DOI: 10.1042/CBI20100919

Source DB:  PubMed          Journal:  Cell Biol Int        ISSN: 1065-6995            Impact factor:   3.612


  6 in total

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2.  Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question.

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Review 3.  Molecular machineries of pH dysregulation in tumor microenvironment: potential targets for cancer therapy.

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5.  Disruption of pH Dynamics Suppresses Proliferation and Potentiates Doxorubicin Cytotoxicity in Breast Cancer Cells.

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Review 6.  Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs--an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research.

Authors:  Salvador Harguindey; Jose Luis Arranz; Julian David Polo Orozco; Cyril Rauch; Stefano Fais; Rosa Angela Cardone; Stephan J Reshkin
Journal:  J Transl Med       Date:  2013-11-06       Impact factor: 5.531

  6 in total

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