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Inhibition of cancer stem cells promoted by Pimozide
Author(s) -
Gonçalves Jussara Maria,
Silva Carolina Amália Barcellos,
Rivero Elena Riet Correa,
Cordeiro Mabel Mariela Rodríguez
Publication year - 2019
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13049
Subject(s) - cancer research , cancer stem cell , wnt signaling pathway , population , medicine , sorafenib , cancer , pharmacology , biology , signal transduction , hepatocellular carcinoma , microbiology and biotechnology , environmental health
Summary Over the past years, studies have described that users of antipsychotics are less likely to develop cancer than the population in general due to cytotoxic properties of this class of drugs on cancer cells. For this reason, Pimozide has been widely studied as a potential anticancer treatment, and satisfactory results in melanoma, central nervous system tumours, osteosarcoma, neuroblastoma, myeloproliferative neoplasms, breast, lung, prostate, ovarian, colorectal, pancreatic, and hepatocellular carcinoma have been showed. Moreover, advantages as clinical use approved by the Food and Drug Administration ( FDA ), high clinical safety, low side effects, and reasonable price have stimulated the treatment with Pimozide instead of other agents. The action mechanism remains unclear, but three vias associated to cancer stem cell ( CSC ) hypothesis show that Pimozide: (a) blocks CSC features, as epithelial‐to‐mesenchymal transition ( EMT ), through inhibition of Wnt‐β/catenin signalling; (b) acts as an inhibitor of signal transducer and activator of transcription ( STAT ‐3 and 5), pathway which is activated and up‐regulated in CSC s; (c) inhibits ubiquitine specific protease ( USP 1) and WD repeat‐containing protein 48 ( WDR 48), that are proteins responsible to inhibit the differentiation and to maintain the cell in an undifferentiated state. Based on this perspective, the aim of this manuscript is to review the antineoplastic role of Pimozide during tumorigenesis and its potential to revert the process of undifferentiation and proliferation of CSC through different vias .