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Pyrvinium pamoate targets to multiple vulnerabilities of Merkel cell carcinoma

ABSTRACT: Pyrvinium pamoate targets to multiple vulnerabilities of Merkel cell carcinoma

PROVIDER: PRJNA955382 | ENA |

REPOSITORIES: ENA

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Pyrvinium pamoate targets to multiple vulnerabilities of Merkel cell carcinoma

Project description:Among several WNT signaling perturbagens, we identified pyrvinium pamoate, an FDA-approved anthelminthic drug that exhibits anti-tumor abilities in multiple cancers. Through the integration of transcriptomic, network, and molecular analyses, we discovered that pyrvinium is broadly effective against Merkel cell carcinoma cell lines, and it targets multiple proposed MCC tumorigenesis pathways. Our study revealed that pyrvinium exerts anti-tumor activity in MCC not only through perturbing the canonical and non-canonical WNT signaling pathway but also non-specifically inhibiting cell growth - via the activation of the p53-mediated apoptosis pathway, modulation of mitochondrial function, and induction of endoplasmic reticulum (ER) stress.

2023-11-06 | GSE229701 | GEO

Identifying Targets of Pyrvinium Pamoate in Jurkat Cells using PISA

Project description:Pyrvinium pamoate, an anthelmintic drug, inhibits mitochondrial biogenesis during initial T-cell activation; however, its molecular target(s) and mechanism of action are unknown. In this study, we treated Jurkat T cell lysate with pyrvinium pamoate (5 nM and 50μM) and used proteome integral solubility alteration (PISA), to identify potential targets.

2023-08-29 | PXD040663 | Pride

MIA-PaCa2 cells treated with Pyrvinium Pamoate, Rotenone, Oligomycin or Control

Project description:Purpose: To compared Pyrvinium Pamoate induced transcription changes with known mitochondrial inhibitors. Methods: MIA-PaCa2 cells were treated with Pyrvinium Pamoate at 0.3µM, Oligomycin at 4µM or rotenone at 0.5 µM for 48 hours and then RNA was collected.

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Effect of pyrvinium pamoate on transcriptome and signaling pathways in FLT3-ITD acute leukemic cell line Molm13

Project description:To identify molecular effects of a classical anthelmintic pyrvinium pamoate(PP), we applied gene expression profiling in human acute leukemic cell line FLT3-ITD+ Molm13 using Whole Transcriptome Shotgun Sequencing (RNA-seq) after 6 h treatment with 50nM or 100nM pyrvinium. We got 94 and 219 differentially expressed genes (DEGs) compared with the control group, respectively. Among 94 DEGs in the 50nM pyrvinium group, 62 were upregulated and 32 were downregulated and corresponded 162 upregulated and 57 downregulated DEGs in the 100nM pyrvinium group.

2021-12-29 | GSE153854 | GEO

Effect of acute pyrvinium pamoate treatment on gene expression of CD4+ T cells during early activation.

Project description:Treatment of T cells with pyrvinium pamoate (PP) early during their activation blocks mitochondrial biogenesis and results in reduced proliferation, skewed CD4+ T cell differentiation and reduced cytokine production. Therefore, to examine the role of PP treatment on mitochondria health, we performed gene expression analysis to identify differentially expressed genes in naive CD4+ T cells cultured with anti-CD3/CD28 plus PP or DMSO. Naive CD4+ T cells were activated for six hours with 2 mg/mL anti-CD3/anti-CD28 mAbs and activated for an additional one hour in the presence or absence of PP.

2023-08-16 | GSE229494 | GEO

MIA-PaCa2 cells treated with Pyrvinium Pamoate, Rotenone, Oligomycin or Control

Project description:MIA-PaCa2 cells treated with Pyrvinium Pamoate, Rotenone, Oligomycin or Control

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Differential gene expression in C. auris in presence of pyrvinium pamoate

Project description:Differential gene expression in C. auris in presence of pyrvinium pamoate

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The antihelmintic drug pyrvinium pamoate targets aggressive breast cancer.

Project description:WNT signaling plays a key role in the self-renewal of tumor initiation cells (TICs). In this study, we used pyrvinium pamoate (PP), an FDA-approved antihelmintic drug that inhibits WNT signaling, to test whether pharmacologic inhibition of WNT signaling can specifically target TICs of aggressive breast cancer cells. SUM-149, an inflammatory breast cancer cell line, and SUM-159, a metaplastic basal-type breast cancer cell line, were used in these studies. We found that PP inhibited primary and secondary mammosphere formation of cancer cells at nanomolar concentrations, at least 10 times less than the dose needed to have a toxic effect on cancer cells. A comparable mammosphere formation IC50 dose to that observed in cancer cell lines was obtained using malignant pleural effusion samples from patients with IBC. A decrease in activity of the TIC surrogate aldehyde dehydrogenase was observed in PP-treated cells, and inhibition of WNT signaling by PP was associated with down-regulation of a panel of markers associated with epithelial-mesenchymal transition. In vivo, intratumoral injection was associated with tumor necrosis, and intraperitoneal injection into mice with tumor xenografts caused significant tumor growth delay and a trend toward decreased lung metastasis. In in vitro mammosphere-based and monolayer-based clonogenic assays, we found that PP radiosensitized cells in monolayer culture but not mammosphere culture. These findings suggest WNT signaling inhibition may be a feasible strategy for targeting aggressive breast cancer. Investigation and modification of the bioavailability and toxicity profile of systemic PP are warranted.

| S-EPMC3754994 | biostudies-literature

Differential gene expression in C. auris in presence of pyrvinium pamoate

Project description:PAT-seq approach was utilised to determine the gene expression in the the transcriptome of C. auris treated with the vehicle DMSO or drug pyrvvinium pamoate (PP). Biological triplicates of C. auris cultures grown in RPMI medium with either DMSO or 1uM PP for 30 minutes at 37 Celsius were havested and total RNA was isolated using standard procedures (hot phenol method).

2022-04-04 | GSE176354 | GEO

Mouse Models of Pediatric Acute Megakaryoblastic Leukemia Reveal Novel Therapeutic Vulnerabilities [DSP750]

Project description:Pediatric acute megakaryoblastic leukemia (AMKL) is an aggressive blood cancer associated with poor therapeutic response and high mortality. We developed CBFA2T3-GLIS2-driven mouse models of AMKL that recapitulate the phenotypic and transcriptional signatures of the human disease. We show that CBFA2T3-GLIS2 and GLIS2 modulate similar transcriptional networks. Oncogenic RAS cooperates with GLIS2 to trigger AMKL, enhancing the penetrance and decreasing the latency of CBFA2T3-GLIS2-dependent AMKL. We find that the FDA-approved drug pyrvinium pamoate, a GLI protein inhibitor, can be repurposed to impair CBFA2T3-GLIS2 levels and promote AMKL cell death. In addition, consistent with our findings that both CBFA2T3-GLIS2 and GLIS2 alter the expression of numerous BH3-only proteins, murine and patient-derived AMKL cells are sensitive to the BCL-2 inhibitor navitoclax. We observe a striking synergistic response to combined treatment with pyrvinium pamoate and navitoclax, suggesting a novel therapeutic option for pediatric patients suffering from CBFA2T3-GLIS2-driven AMKL.

2023-08-04 | GSE208186 | GEO

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