Closantel Suppresses Angiogenesis and Cancer Growth in Zebrafish Models

Zhu, Xiaoyu; Xia, Bo; Liu, Hong-Cui; Xu, Yiqiao; Huang, Changjiang; Gao, Jimin; Dong, Qian; Li, Chunqi

doi:10.1089/adt.2015.679

Cited by 22 publications

(11 citation statements)

References 38 publications

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“…Closantel is a salicylanilide derivative and is considered to be an anthelmintic agent in livestock [42]. The antiangiogenesis and anticancer effects of Closantel sodium and Closantel have also been previously reported [43]. However, to our knowledge, neither the antiviral activity nor the antiviral mechanisms of Closantel sodium and Closantel have been reported before.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Antiviral Drug Candidates on Canine Parvovirus in F81 cells

Zhou

Lin

et al. 2019

Viruses

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Canine parvovirus (CPV) is a common etiological agent of acute enteritis, which occurs globally in domestic and wild carnivores. Despite the widespread use of inactivated or live attenuated vaccines, the emergence of antigenic variants and the influence of maternal antibodies have raised some concerns regarding the efficacy of commercial vaccines. While no specific antiviral therapy for CPV infection exists, the only treatment option for the infection is supportive therapy based on symptoms. Thus, there is an urgent medical need to develop antiviral therapeutic options to reduce the burden of CPV-related disease. In this study, a cytopathic effect (CPE)-based high-throughput screening assay was used to screen CPV inhibitors from a Food and Drug Administration (FDA)-approved drug library. After two rounds of screening, seven out of 1430 screened drugs were found to have >50% CPE inhibition. Three drugs—Nitazoxanide, Closantel Sodium, and Closantel—with higher anti-CPV effects were further evaluated in F81 cells by absolute PCR quantification and indirect immunofluorescence assay (IFA). The inhibitory effects of all three drugs were dose-dependent. Time of addition assay indicated that the drugs inhibited the early processes of the CPV replication cycle, and the inhibition effects were relatively high within 2 h postinfection. Western blot assay also showed that the three drugs had broad-spectrum antiviral activity against different subspecies of three CPV variants. In addition, antiapoptotic effects were observed within 12 h in Nitazoxanide-treated F81 cells regardless of CPV infection, while Closantel Sodium- or Closantel-treated cells had no pro- or antiapoptotic effects. In conclusion, Nitazoxanide, Closantel Sodium, and Closantel can effectively inhibit different subspecies of CPV. Since the safety profiles of FDA-approved drugs have already been extensively studied, these three drugs can potentially become specific and effective anti-CPV drugs.

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Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Antiviral Drug Candidates on Canine Parvovirus in F81 cells

Zhou

Lin

et al. 2019

Viruses

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“…The embryos were washed and staged at 6 and 24 hpf (hours post fertilization). The zebrafish facility at Hunter Biotechnology, Inc., is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International (Zhu, Xu, Guo, & Li, 2015; Zhu, Liu, et al, 2016; Zhu, Xia, et al, 2016).…”

Section: Methodsmentioning

confidence: 99%

Cardiotoxicity induced by Cochinchina momordica seed extract in zebrafish

Xia

Huang³

et al. 2021

J of Applied Toxicology

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Momordica cochinchinensis (Lour.) Spreng is an indigenous South Asian edible fruit, and seeds of Momordica cochinchinensis have been used therapeutically in traditional Chinese medicine. Previous studies have shown that M. cochinchinensis seed (Momordicae Semen) has various pharmaceutical properties such as antioxidant and anti‐ulcer effects as well as contains secondary metabolites with potential anticancer activities such as triterpenoids and saponins. Recent studies reported that water extract and ethanol extract of M. cochinchinensi seed were tested on mammals using an acute toxic classic method as OECD guidelines 420. No matter injected intravenously or intramuscularly, animals died within several days. In this study, zebrafish embryos were exposed to various doses of Cochinchina momordica seed extract (CMSE) from 2 dpf (days post fertilization, dpf) to 3 dpf. CMSE‐induced cardiotoxicity such as pericardial edema, cardiac apoptosis, increased ROS production, cardiac neutrophil infiltration, decreased blood flow velocity, and reduced expression of three marker genes of cardiac functions were found in zebrafish roughly in a dose‐dependent manner. These results suggest that CMSE may induce cardiotoxicity through pathways involved in inflammation, oxidative stress, and apoptosis.

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“…Closantel is another halogenated salicylamide agent reported to inhibit BRAF V600E [71]. Closantel (0.025-10 µM) showed anti-angiogenic and anti-tumor properties in zebrafish and significantly inhibited cell proliferation in zebrafish xenotransplanted with human tumor cells, including liver and pancreatic cancer cells [44]. However, further studies in experimental and preclinical models are required to confirm closantel's anti-cancer effects and provide new clues about its possible clinical application.…”

Section: Closantelmentioning

confidence: 99%

Repositioning of Anthelmintic Drugs for the Treatment of Cancers of the Digestive System

Laudisi

Marônek

Grazia

et al. 2020

IJMS

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Tumors of the digestive system, when combined together, account for more new cases and deaths per year than tumors arising in any other system of the body and their incidence continues to increase. Despite major efforts aimed at discovering and validating novel and effective drugs against these malignancies, the process of developing such drugs remains lengthy and costly, with high attrition rates. Drug repositioning (also known as drug repurposing), that is, the process of finding new uses for approved drugs, has been gaining popularity in oncological drug development as it provides the opportunity to expedite promising anti-cancer agents into clinical trials. Among the drugs considered for repurposing in oncology, compounds belonging to some classes of anthelmintics—a group of agents acting against infections caused by parasitic worms (helminths) that colonize the mammalian intestine—have shown pronounced anti-tumor activities and attracted particular attention due to their ability to target key oncogenic signal transduction pathways. In this review, we summarize and discuss the available experimental and clinical evidence about the use of anthelmintic drugs for the treatment of cancers of the digestive system.

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Closantel Suppresses Angiogenesis and Cancer Growth in Zebrafish Models

Cited by 22 publications

References 38 publications

Inhibitory Effects of Antiviral Drug Candidates on Canine Parvovirus in F81 cells

Inhibitory Effects of Antiviral Drug Candidates on Canine Parvovirus in F81 cells

Cardiotoxicity induced by Cochinchina momordica seed extract in zebrafish

Repositioning of Anthelmintic Drugs for the Treatment of Cancers of the Digestive System

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