New study below [1].
Pimozide is an antipsychotic drug [2].
"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 Tumors, Osteosarcoma, Neuroblastoma, Myeloproliferative Neoplasms, Breast, Lung, Prostate, Ovarian, Colorectal, Pancreatic, and Hepatocellular Carcinoma have been showed. Moreover, advantages as clinical use approved by Food and Drug Administration (FDA), high clinical safety, low side effects, and reasonable price have stimulated the treatment with Pimozide instead of other agents." [1]
There has been a lot of interest in STAT3 in recent years - 550 PubMed hits for <prostate stat3> in twenty years!
From 2017 [3]:
"Mechanisms of castration-resistant prostate cancer (CRPC) are not well understood, thus hindering rational-based drug design. Activation of STAT3/5A, key components of the JAK/STAT pathway, is implicated in aggressive PC, yet their clinical relevance in CRPC remains elusive. Here, we evaluated the possible role of STAT3/5A in CRPC using immunological, quantitative mRNA expression profiling, and pharmacological methods. We observed a strong nuclear immunoreactivity for STAT3 and STAT5A in 93% (n=14/15) and 80% (n=12/15) of CRPC cases, respectively, compared with benign prostatic hyperplasia (BPH). We demonstrated that PC cells express varying levels of STAT3 and STAT5A transcripts. In addition, we demonstrate that pimozide, a psychotropic drug and an indirect inhibitor of STAT5, attenuated PC cells growth, and induced apoptosis in a dose-dependent manner. Furthermore, our analysis of the PC public data revealed that the STAT3/5A genes were frequently amplified in metastatic CRPC."
From 2016 [4]:
"Currently, drug discovery and development for clinical treatment of prostate cancer has received increased attention, specifically the STAT3 inhibitor. Our previous study reported that the neuroleptic drug pimozide had antitumor activity against hepatocellular carcinoma cells or stem-like cells through suppressing the STAT3 activity. In the present study we demonstrate that pimozide inhibits cell growth and cellular STAT3 activation in prostate cancer cells. Our results showed that pimozide inhibited prostate cancer cell proliferation in a dose- and time-dependent manner by inducing G1 phase cell cycle arrest, downregulated the ability of colony formation and sphere forming, as well as suppressed cells migration in both DU145 and LNCaP cells. Surprisingly, pimozide reduced the basal expression of phosphorylation STAT3 at tyrosine 705 and reversed the expression of phosphorylation of STAT3 induced by IL-6 addition, suggesting that pimozide can suppress cellular STAT3 activation. Thus, the antipsychotic agent pimozide may be a potential and novel therapeutic for patients with advanced prostate cancer."
From the new paper [1]:
"The action mechanism {of Pimozide} remains unclear, but three vias associated to cancer stem cell (CSC) hypothesis show that Pimozide: 1) blocks CSC features, as epithelial-to-mesenchymal transition (EMT), through inhibition of Wnt-β/catenin signaling; 2) acts as an inhibitor of Signal Transducer and Activator of Transcription (STAT-3 and 5), pathway which is activated and up-regulated in CSCs; 3) 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 was to review the anti-neoplastic role of Pimozide during the tumorigenesis and its potential in revert the process of undifferentiation and proliferation of CSC through different vias."
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/303...
[2] en.wikipedia.org/wiki/Pimozide
