Short Report

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 FreiseAffiliated withDepartment of Gastroenterology, Infectiology and Rheumatology, Campus Benjamin Franklin, Charité - Universitätsmedizin BerlinCenter for Cardiovascular Research, Campus Mitte, Charité - Universitätsmedizin Berlin Email author 
  • , Martin RuehlAffiliated withDepartment of Gastroenterology, Infectiology and Rheumatology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin
  • , Daniel SeehoferAffiliated withDepartment of General, Visceral and Transplantation Surgery, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin
  • , Joachim HoyerAffiliated withDepartment of Nephrology, Philipps-Universität Marburg
  • , Rajan SomasundaramAffiliated withDepartment of Gastroenterology, Infectiology and Rheumatology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin

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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