Investigational New Drugs

, Volume 31, Issue 2, pp 452–457

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

DOI: 10.1007/s10637-012-9879-6

Cite this article as:
Freise, C., Ruehl, M., Seehofer, D. et al. Invest New Drugs (2013) 31: 452. doi:10.1007/s10637-012-9879-6

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

IKCaKCNN4HCCTRAM-34ESR1NF-κB

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