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Int J Biol Sci 2016; 12(7):768-775. doi:10.7150/ijbs.14718 This issue Cite

Research Paper

Inhibition of wnt/β-catenin Signaling in Hepatocellular Carcinoma by an Antipsychotic Drug Pimozide

Valerie Fako¹, Zhipeng Yu¹, Curtis J. Henrich^{2, 3}, Tanya Ransom², Anuradha S. Budhu^1✉, Xin W. Wang^1✉

1. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA;
2. Molecular Targets Laboratory, National Cancer Institute, Frederick, Maryland 21702, USA;
3. Basic Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.

✉ Corresponding author: Anuradha Budhu or Xin Wei Wang, National Cancer Institute, 37 Convent Drive, Building 37, Room 3044A, Bethesda, Maryland 20892; Email: xw3ugov; Phone: 301-496-2099.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common forms of malignant cancers in the world, yet very few effective systemic treatments for HCC patients exist. Thus, the development of new treatment modalities presents a great need. The wnt/β-catenin signaling pathway is highly activated in stem cell-like aggressive HCC, which is associated with chemoresistance and poor survival in HCC patients. In a previous study, we found that an FDA-approved psychiatric drug, pimozide (PMZ), has anti-cancer properties in HCC cell lines that express epithelial cell adhesion molecule (EpCAM), a hepatic stem cell marker that is a functional down-stream target of the wnt/β-catenin pathway. In this study, we demonstrate that PMZ effectively inhibits cell growth of HCC cells by disrupting the wnt/β-catenin signaling pathway and reducing EpCAM expression. Thus, PMZ may be a useful molecular entity that could be repurposed as an anti-cancer therapy for treatment of HCC.

Keywords: Pimozide, wnt/β-catenin, EpCAM, HCC.

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