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Invest New Drugs. 2013 Apr;31(2):452-7. doi: 10.1007/s10637-012-9879-6. Epub 2012 Oct 2.

The inhibitor of Ca(2+)-dependent K+ channels TRAM-34 blocks growth of hepatocellular carcinoma cells via downregulation of estrogen receptor alpha mRNA and nuclear factor-kappaB.

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  • 1Department of Gastroenterology, Infectiology and Rheumatology, Campus Benjamin Franklin, Charit√© - Universit√§tsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany. christian.freise@charite.de

Abstract

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.

PMID:
23054207
[PubMed - indexed for MEDLINE]
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