Inhibition of wnt/β-catenin Signaling in Hepatocellular Carcinoma by an Antipsychotic Drug Pimozide.
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.
1. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA;
Valerie
V
Fako
1. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA;
Zhipeng
Z
Yu
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.
Curtis J
CJ
Henrich
2. Molecular Targets Laboratory, National Cancer Institute, Frederick, Maryland 21702, USA;
Tanya
T
Ransom
1. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA;
Anuradha S
AS
Budhu
1. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA;
Xin W
XW
Wang
D014150:Antipsychotic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D010868:Pimozide / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D014150:Antipsychotic Agents; D000071858:Epithelial Cell Adhesion Molecule; D051153:Wnt Proteins; D051176:beta Catenin; D010868:Pimozide
EpCAM; HCC.; Pimozide; wnt/β-catenin