Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 12, Issue 7, Pages 768-775Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.14718
Keywords
Pimozide; wnt/beta-catenin; EpCAM; HCC
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Funding
- Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research and Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]
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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/beta-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/beta-catenin pathway. In this study, we demonstrate that PMZ effectively inhibits cell growth of HCC cells by disrupting the wnt/beta-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.
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