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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

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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.

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Acknowledgments

This work was supported by the Collaborative Research Center (SFB633 Z1) from the Deutsche Forschungsgemeinschaft, the Berliner Sparkassenstiftung Medizin and the Monika Kutzner Stiftung. TRAM-34 was kindly supplied by Dr. Heike Wulff, Department of Pharmacology, University of California, Davis, CA, USA

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The authors declare that they have no conflict of interest.

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Correspondence to Christian Freise.

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Freise, C., Ruehl, M., Seehofer, D. et al. 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. Invest New Drugs 31, 452–457 (2013). https://doi.org/10.1007/s10637-012-9879-6

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  • DOI: https://doi.org/10.1007/s10637-012-9879-6

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