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

Fako, Valerie; Yu, Zhipeng; Henrich, Curtis J.; Ransom, Tanya T.; Budhu, Anuradha; Wang, Xin Wei

doi:10.7150/ijbs.14718

Cited by 49 publications

(33 citation statements)

References 34 publications

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“…Fako et al confirmed that Pimozide effectively inhibited cell growth of HCC cells by disrupting the wnt/β‐catenin signalling pathway and reducing EpCAM expression. They demonstrated that this pathway is a possible target for the development of new chemotherapeutics …”

Section: Mechanism Of Action Of Pimozide In Cancermentioning

confidence: 98%

“…Additionally, Pimozide has showed an anticancer effect on other types of cancer: melanoma, CNS tumours, osteosarcoma, neuroblastoma, myeloproliferative neoplasms, breast, lung, prostate, ovarian, colorectal, pancreatic and hepatocellular carcinoma . Although, patients with mental disorders such as schizophrenia are less likely to develop cancer than the general population, there are yet no reports about the cancer incidence specifically in Pimozide users.…”

Section: Pimozidementioning

confidence: 99%

“…Fako et al described anticancer activity in HCC cell lines that expressed epithelial cell adhesion molecule (EpCAM), a hepatic stem cell marker, that is a functional downstream target of the wnt/β‐catenin pathway. According to Chen et al and Fako et al Pimozide could be a novel drug to cancer therapy.…”

Section: Pimozide As a Potential Anticancer Agentmentioning

confidence: 99%

“…Epithelial‐to‐mesenchymal transition requires that cells lose their epithelial characteristics and acquire more mesenchymal‐like phenotypes, including alterations related to EpCAM, a stem cell marker that is a direct downstream transcriptional target of wnt/β‐catenin signalling . Fako et al confirmed that Pimozide effectively inhibited cell growth of HCC cells by disrupting the wnt/β‐catenin signalling pathway and reducing EpCAM expression. They demonstrated that this pathway is a possible target for the development of new chemotherapeutics …”

Section: Mechanism Of Action Of Pimozide In Cancermentioning

confidence: 99%

“…Pimozide, an orally active antipsychotic agent used to treat Tourette's syndrome, chronic psychosis, resistant phonic, and motor tics, has been widely indicated as a potential anticancer agent . All studies that used Pimozide as an anti‐tumour drug showed positive results, mainly against CSC, which are responsible for chemoresistance …”

Section: Introductionmentioning

confidence: 99%

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Inhibition of cancer stem cells promoted by Pimozide

Gonçalves

Silva

Rivero

et al. 2018

Clin Exp Pharma Physio

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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 CSCs; (c) inhibits ubiquitine specific protease (USP1) and WD repeat‐containing protein 48 (WDR48), 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.

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Section: Mechanism Of Action Of Pimozide In Cancermentioning

confidence: 98%

Section: Pimozidementioning

confidence: 99%

Section: Pimozide As a Potential Anticancer Agentmentioning

confidence: 99%

Section: Mechanism Of Action Of Pimozide In Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Inhibition of cancer stem cells promoted by Pimozide

Gonçalves

Silva

Rivero

et al. 2018

Clin Exp Pharma Physio

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Propofol‐induced miR‐219‐5p inhibits growth and invasion of hepatocellular carcinoma through suppression of GPC3‐mediated Wnt/β‐catenin signalling activation

Gong

Xue

Deng

et al. 2019

J of Cellular Biochemistry

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Propofol is one of the most extensively used intravenous anaesthetic agents, which has been found to improve the surgical intervention outcome of several types of cancer, including hepatocellular carcinoma (HCC). Additionally, in vitro and in vivo experiments have also indicated that propofol affects the biological behaviour of HCC. However, the underlying mechanisms of the surgical resection of HCC with propofol have not been fully understood. In the present study, we aimed to investigate the underlying mechanism of propofol inhibition of the growth and invasion of HCC cells. Our results showed that treatment with propofol suppressed the proliferation, invasion and migration of HCC in vitro. The subcutaneous xenograft tumour and orthotopic xenograft tumour experiments in nude mice showed that propofol significantly decreased tumour volumes, growth rates and the liver orthotopic xenograft tumour in vivo. Furthermore, the underlying mechanism investigations of the suppressive effects of propofol on HCC cells revealed that propofol treatment upregulated the expression levels of the candidate tumour suppressor miR‐219‐5p. Silencing of propofol‐induced miR‐219‐5p using anti‐miR‐219‐5p abrogated the inhibitory effects on the proliferation, migration and invasion of HCC cells exerted by propofol treatment. Additionally, we demonstrated that propofol reversed the epithelial‐mesenchymal transition of Huh7 and SMMC7721 cells via miR‐219‐5p induction. The molecular mechanism behind these findings is that propofol‐induced miR‐219‐5p inhibits HCC cell progression by targeting glypican‐3 and subsequently results in the inhibition of Wnt/β‐catenin signalling. Taken together, our study provides new insights into the advantages of the surgical intervention of HCC with propofol anaesthetization.

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TNIK influence the effects of antipsychotics on Wnt/β-catenin signaling pathway

Yuan

et al. 2021

Psychopharmacology

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

Cited by 49 publications

References 34 publications

Inhibition of cancer stem cells promoted by Pimozide

Inhibition of cancer stem cells promoted by Pimozide

Propofol‐induced miR‐219‐5p inhibits growth and invasion of hepatocellular carcinoma through suppression of GPC3‐mediated Wnt/β‐catenin signalling activation

TNIK influence the effects of antipsychotics on Wnt/β-catenin signaling pathway

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