Medical Oncology

, Volume 29, Issue 3, pp 2127–2135 | Cite as

Imatinib has the potential to exert its antileukemia effects by down-regulating hERG1 K+ channels in chronic myelogenous leukemia

  • Fang Zheng
  • Huiyu Li
  • Kaiwei Liang
  • Yimei Du
  • Dongmei Guo
  • Shiang Huang
Original Paper
First Online:
Received:
Accepted:

Abstract

Imatinib is a powerful protein tyrosine kinase (PTK) inhibitor that specifically targets BCR-ABL, KIT, and PDGFR kinases, has become the current first-line therapy for all newly diagnosed chronic myeloid leukemia (CML). Beside PTKs, PTK inhibitors alter the activity of a large number of voltage-dependent ion channels. hERG1 K+ channels are highly expressed in leukemia cells and appear of exceptional importance in favoring leukemogenesis. The present study explored a possible regulatory effect of imatinib upon hERG1 K+ channels as a means to uncover new molecular events involved in the antileukemic activity of this PTK inhibitor in CML. The results demonstrated that hERG1 was highly detected in K562 cells and primary CML cells, and down-regulated by imatinib at mRNA and protein levels. Furthermore, imatinib markedly reduced hERG currents in HEK293T-hERG cells, this effect was accompanied by inhibition of CML cell proliferation and apoptosis, as well as suppression of vascular endothelial growth factor (VEGF) secretion. Moreover, these antileukemia effects of imatinib were potentiated by E-4031, a specific hERG1 inhibitor. Together, these results provide evidence of a novel potential molecular mechanism of antileukemic activities by imatinib which, independent of targeting tyrosine kinase, highlight hERG1 K+ channels as a therapeutic target for CML treatment.

Keywords

hERG channel Imatinib VEGF Chronic myeloid leukemia 
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Notes

Acknowledgments

The financial support of this work is received from the National Nature Sciences Foundation of China (No. 30971112).

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Fang Zheng
    • 1
  • Huiyu Li
    • 1
  • Kaiwei Liang
    • 1
  • Yimei Du
    • 2
  • Dongmei Guo
    • 1
  • Shiang Huang
    • 1
  1. 1.Center for Stem Cell Research and Application, Institute of Hematology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  2. 2.Research Center of Ion Channelopathy, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China

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