Pyrvinium Pamoate

2021 ◽  
Keyword(s):  
Pyrvinium Pamoate

scholarly journals Pyrvinium pamoate inhibits cell proliferation through ROS-mediated AKT-dependent signaling pathway in colorectal cancer

2021 ◽  
Vol 38 (2) ◽  
Author(s):  
Wenqian Zheng ◽  
Jinhui Hu ◽  
Yiming Lv ◽  
Bingjun Bai ◽  
Lina Shan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Flow Cytometric Analysis ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Dependent Signaling Pathway ◽  
Pyrvinium Pamoate

AbstractThe use of the anthelmintic drug pyrvinium pamoate (PP) in cancer therapy has been extensively investigated in the last decade. PP has been shown to have an inhibitory effect in colorectal cancer (CRC), but the underlying mechanism remains elusive. We aimed to investigate the antitumor activity and mechanisms of PP in CRC. In the present study, we used CCK-8 assays, colony formation assays, and western blotting to reveal that PP effectively suppressed CRC cell proliferation and the AKT-dependent signaling pathway in a concentration-dependent and time-dependent manner. Flow cytometric analysis and fluorescence microscopy demonstrated that PP increased intracellular reactive oxygen species (ROS) accumulation. We found that the inhibitory effect of PP on cell proliferation and AKT protein expression induced by PP could be partially reversed by N-acetyl-l-cysteine (NAC), an ROS scavenger. In addition, the results also demonstrated that PP inhibited cell migration by modulating epithelial-to-mesenchymal transition (EMT)-related proteins, including E-cadherin and vimentin. In conclusion, our data suggested that PP effectively inhibited cell proliferation through the ROS-mediated AKT-dependent signaling pathway in CRC, further providing evidence for the use of PP as an antitumor agent.

Mitochondria as a potential target for the development of prophylactic and therapeutic drugs against Schistosoma mansoni infection

2021 ◽  
Author(s):  
Keith Kiplangat Talaam ◽  
Daniel Ken Inaoka ◽  
Takeshi Hatta ◽  
Daigo Tsubokawa ◽  
Naotoshi Tsuji ◽  
...  
Keyword(s):  
Drug Development ◽  
Schistosoma Mansoni ◽  
Worm Burden ◽  
Consumption Rate ◽  
Therapeutic Agent ◽  
Ex Vivo ◽  
Prophylactic Agent ◽  
Therapeutic Drugs ◽  
Pyrvinium Pamoate

Emergence of parasites resistant to praziquantel, the only therapeutic agent, and its ineffectiveness as a prophylactic agent (inactive against the migratory/juvenile Schistosoma mansoni ), makes the development of new antischistosomal drugs urgent. The parasite’s mitochondrion is an attractive target for drug development because this organelle is essential for survival throughout the parasite’s life cycle. We investigated the effects of 116 compounds against Schistosoma mansoni cercariae motility that have been reported to affect mitochondria-related processes in other organisms. Next, eight compounds plus two controls (mefloquine and praziquantel) were selected and assayed against motility of schistosomula ( in vitro ) and adults ( ex vivo ). Prophylactic and therapeutic assays were performed using infected mouse models. Inhibition of oxygen consumption rate (OCR) was assayed using Seahorse XFe24 Analyzer. All selected compounds showed excellent prophylactic activity, reducing the worm burden in the lungs to less than 15% that obtained in the vehicle control. Notably, ascofuranone showed the highest activity with a 98% reduction of the worm burden, suggesting the potential for development of ascofuranone as a prophylactic agent. The worm burden of infected mice with S. mansoni at the adult stage was reduced by more than 50% in mice treated with mefloquine, nitazoxanide, amiodarone, ascofuranone, pyrvinium pamoate, or plumbagin. Moreover, adult mitochondrial OCR was severely inhibited by ascofuranone, atovaquone, and nitazoxanide, while pyrvinium pamoate inhibited both mitochondrial and non-mitochondrial OCRs. These results demonstrate that the mitochondria of S. mansoni are feasible target for drug development.

scholarly journals β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Catherina A. Cuevas ◽  
Cheril Tapia-Rojas ◽  
Carlos Cespedes ◽  
Nibaldo C. Inestrosa ◽  
Carlos P. Vio
Keyword(s):  
Blood Pressure ◽  
Signal Transduction ◽  
Single Dose ◽  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Target Genes ◽  
Hypertensive Rats ◽  
Collagen Types ◽  
Dependent Signaling Pathway ◽  
Pyrvinium Pamoate

The mechanism of hypertension-induced renal fibrosis is not well understood, although it is established that high levels of angiotensin II contribute to the effect. Sinceβ-catenin signal transduction participates in fibrotic processes, we evaluated the contribution ofβ-catenin-dependent signaling pathway in hypertension-induced renal fibrosis. Two-kidney one-clip (2K1C) hypertensive rats were treated with lisinopril (10 mg/kg/day for four weeks) or with pyrvinium pamoate (Wnt signaling inhibitor, single dose of 60 ug/kg, every 3 days for 2 weeks). The treatment with lisinopril reduced the systolic blood pressure from 220 ± 4 in 2K1C rats to 112 ± 5 mmHg (P<0.05), whereas the reduction in blood pressure with pyrvinium pamoate was not significant (212 ± 6 in 2K1C rats to 170 ± 3 mmHg,P>0.05). The levels of collagen types I and III, osteopontin, and fibronectin decreased in the unclipped kidney in both treatments compared with 2K1C rats. The expressions ofβ-catenin, p-Ser9-GSK-3beta, and theβ-catenin target genes cyclin D1, c-myc, and bcl-2 significantly decreased in unclipped kidney in both treatments (P<0.05). In this study we provided evidence thatβ-catenin-dependent signaling pathway participates in the renal fibrosis induced in 2K1C rats.

129 – Repurposing the Fda Approved Drug Pyrvinium Pamoate to Target Hur in Pancreatic Ductal Adenocarcinoma

2019 ◽  
Vol 156 (6) ◽  
pp. S-1376-S-1377
Author(s):  
Christopher Schultz ◽  
Teena Dhir ◽  
Alex Haber ◽  
Wei Jiang ◽  
Saswati N. Chand ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Pyrvinium Pamoate

The impact of pyrvinium pamoate on colon cancer cell viability

2014 ◽  
Vol 29 (10) ◽  
pp. 1189-1198 ◽  
Author(s):  
Armin Wiegering ◽  
Friedrich-Wilhelm Uthe ◽  
Melanie Hüttenrauch ◽  
Bettina Mühling ◽  
Michael Linnebacher ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Viability ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
The Impact ◽  
Pyrvinium Pamoate

scholarly journals Identification of FDA-Approved Drugs with Activity against Stationary Phase Bartonella henselae

Antibiotics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 50 ◽  
Author(s):  
Tingting Li ◽  
Jie Feng ◽  
Shuzhen Xiao ◽  
Wanliang Shi ◽  
David Sullivan ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Stationary Phase ◽  
Drug Exposure ◽  
Bartonella Henselae ◽  
Drug Candidates ◽  
Persistent Infections ◽  
Viability Assay ◽  
Approved Drugs ◽  
Pyrvinium Pamoate ◽  
Effective Treatments

Bartonella henselae can cause various infections in humans, ranging from benign and self-limiting diseases to severe and life-threatening diseases as well as persistent infections that are difficult to treat. To develop more effective treatments for persistent Bartonella infections, in this study, we performed a high-throughput screen of an FDA-approved drug library against stationary phase B. henselae using the SYBR Green I/propidium iodide (PI) viability assay. We identified 110 drug candidates that had better activity against stationary phase B. henselae than ciprofloxacin, and among the top 52 drug candidates tested, 41 drugs were confirmed by microscopy to have higher activity than the current frontline antibiotic erythromycin. The identified top drug candidates include pyrvinium pamoate, daptomycin, methylene blue, azole drugs (clotrimazole, miconazole, sulconazole, econazole, oxiconazole, butoconazole, bifonazole), aminoglycosides (gentamicin and streptomycin, amikacin, kanamycin), amifostine (Ethyol), antiviral Lopinavir/ritonavir, colistin, nitroxoline, nitrofurantoin, verteporfin, pentamidine, berberine, aprepitant, olsalazine, clinafloxacin, and clofoctol. Pyrvinium pamoate, daptomycin, methylene blue, clotrimazole, and gentamicin and streptomycin at their respective maximum drug concentration in serum (Cmax) had the capacity to completely eradicate stationary phase B. henselae after 3-day drug exposure in subculture studies. While the currently used drugs for treating bartonellosis, including rifampin, erythromycin, azithromycin, doxycycline, and ciprofloxacin, had very low minimal inhibitory concentration (MIC) against growing B. henselae, they had relatively poor activity against stationary phase B. henselae, except aminoglycosides. The identified FDA-approved agents with activity against stationary phase B. henselae should facilitate development of more effective treatments for persistent Bartonella infections.

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