Investigational New Drugs

, Volume 31, Issue 2, pp 452–457 | Cite as

The inhibitor of Ca2+-dependent K+ channels TRAM-34 blocks growth of hepatocellular carcinoma cells via downregulation of estrogen receptor alpha mRNA and nuclear factor-kappaB

  • Christian Freise
  • Martin Ruehl
  • Daniel Seehofer
  • Joachim Hoyer
  • Rajan Somasundaram
Short Report

Summary

Hepatocellular carcinoma (HCC) is the most common liver malignancy still demanding for novel therapeutic options. Since the ion channel inhibitor TRAM-34 (1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole) was shown to block growth in various cancer cells, we investigated anti-tumor effects of TRAM-34 in human HCC cell lines. We found that TRAM-34 reduced HCC cell proliferation without induction of apoptosis. This was due to a decreased mRNA expression of estrogen receptor alpha (ESR1) and a reduced activation of NF-kappaB, which both are implicated in the development of HCC. Therefore, TRAM-34 might represent a novel therapeutic target for the treatment of HCC.

Keywords

IKCa KCNN4 HCC TRAM-34 ESR1 NF-κB 

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Christian Freise
    • 1
    • 4
  • Martin Ruehl
    • 1
  • Daniel Seehofer
    • 2
  • Joachim Hoyer
    • 3
  • Rajan Somasundaram
    • 1
  1. 1.Department of Gastroenterology, Infectiology and Rheumatology, Campus Benjamin FranklinCharité - Universitätsmedizin BerlinBerlinGermany
  2. 2.Department of General, Visceral and Transplantation Surgery, Campus Virchow KlinikumCharité - Universitätsmedizin BerlinBerlinGermany
  3. 3.Department of NephrologyPhilipps-Universität MarburgMarburgGermany
  4. 4.Center for Cardiovascular Research, Campus MitteCharité - Universitätsmedizin BerlinBerlinGermany

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