Repurposing of Anthelminthics as Anticancer Drugs

Hamilton, Gerhard; Rath, Barbara H.

doi:10.7150/oncm.20563

Cited by 19 publications

(34 citation statements)

References 81 publications

(170 reference statements)

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“…Although the lack of toxicity in this short-term experimental treatment with MBZ does not necessarily reflect long-term toxicity, other studies have demonstrated the favorable toxicity profile of MBZ over long periods. 39…”

Section: Discussionmentioning

confidence: 99%

Mebendazole Potentiates Radiation Therapy in Triple-Negative Breast Cancer

Zhang

Dratver

Yazal

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

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Section: Discussionmentioning

confidence: 99%

Mebendazole Potentiates Radiation Therapy in Triple-Negative Breast Cancer

Zhang

Dratver

Yazal

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

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“…The mitochondrial uncoupling activity of niclosamide can reduce intracellular ATP (Hamilton and Rath, 2017). Here, we revealed that niclosamide-and temsirolimus-treated cells depleted intracellular ATP levels (Figure 11).…”

Section: Expression Of the Mtorc1 Signaling Pathway And Hiv-1 Proteinmentioning

confidence: 68%

Inhibition of human immunodeficiency virus type 1 by niclosamide through mTORC1 inhibition

Niyomdecha

Suptawiwat

Boonarkart

et al. 2020

Heliyon

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Niclosamide has been known to inhibit a number of pH-dependent viruses via the neutralization of endosomal acidic pH. It has also been shown to disrupt the mTORC1 signaling pathway. The replication of many viruses requires mTORC1 activation. Here, we investigated the inhibitory activity of niclosamide against HIV-1, and determined whether mTORC1 inhibition was involved. The cytotoxicity and anti-HIV-1 activity of niclosamide were tested in TZM-bl and SupT1 cells. Niclosamide showed a dose-and time-dependent inhibitory activity against HIV-1 replication, but the inhibition did not involve the reverse transcription and transcription steps. The mechanism of mTORC1 inhibition was explored by using MHY1485, an mTORC1 activator, to reverse the mTORC1 inhibition, which could partially restore HIV-1 replication. In addition, niclosamide was found to downregulate mTORC1 via AMPK activation, resulting in a decreased phosphorylation of the downstream substrates of S6K and 4EBP1. Niclosamide could also reduce the synthesis of HIV-1 p24 protein. Likewise, MHY-1485 could partially reverse the inhibitory effect of niclosamide by increasing the phosphorylation in the mTORC1 pathway and HIV-1 viral protein synthesis. Our findings, therefore, demonstrated the antiviral mechanism of niclosamide is via the AMPK-mTORC1 pathway, which could be a common therapeutic target for various viruses.

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“…Furthermore, cestode resistance was associated with Wnt/β-catenin signaling and with networks linked to digestive system development and function, and with cellular morphology and abnormalities. Interestingly, cestode infections can be treated with anthelmintic drugs such as niclosamide (Katz, 1977), mebendazole or pyrvinium (Hamilton and Rath, 2017), which are also used to treat Wnt-dependent cancers (Lu et al, 2011;Osada et al, 2011;Zhang et al, 2017) due to their Wnt inhibitory action (Chen et al, 2009). These results suggest a potential involvement of the Wnt signaling pathway to cestode parasitism resistance.…”

Section: Discussionmentioning

confidence: 99%

Integrating Genetic and Genomic Analyses of Combined Health Data Across Ecotypes to Improve Disease Resistance in Indigenous African Chickens

et al. 2020

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Poultry play an important role in the agriculture of many African countries. The majority of chickens in sub-Saharan Africa are indigenous, raised in villages under semi-scavenging conditions. Vaccinations and biosecurity measures rarely apply, and infectious diseases remain a major cause of mortality and reduced productivity. Genomic selection for disease resistance offers a potentially sustainable solution but this requires sufficient numbers of individual birds with genomic and phenotypic data, which is often a challenge to collect in the small populations of indigenous chicken ecotypes. The use of information across-ecotypes presents an attractive possibility to increase the relevant numbers and the accuracy of genomic selection. In this study, we performed a joint analysis of two distinct Ethiopian indigenous chicken ecotypes to investigate the genomic architecture of important health and productivity traits and explore the feasibility of conducting genomic selection across-ecotype. Phenotypic traits considered were antibody response to Infectious Bursal Disease (IBDV), Marek's Disease (MDV), Fowl Cholera (PM) and Fowl Typhoid (SG), resistance to Eimeria and cestode parasitism, and productivity [body weight and body condition score (BCS)]. Combined data from the two chicken ecotypes, Horro (n = 384) and Jarso (n = 376), were jointly analyzed for genetic parameter estimation, genome-wide association studies (GWAS), genomic breeding value (GEBVs) calculation, genomic predictions, whole-genome sequencing (WGS), and pathways analyses. Estimates of across-ecotype heritability were significant and moderate in magnitude (0.22-0.47) for all traits except for SG and BCS. GWAS identified several significant genomic associations with health and productivity traits. The WGS analysis revealed putative candidate genes and mutations for IBDV (TOLLIP, ANGPTL5, BCL9, THEMIS2), MDV (GRM7), SG (MAP3K21), Eimeria (TOM1L1) and

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Repurposing of Anthelminthics as Anticancer Drugs

Cited by 19 publications

References 81 publications

Mebendazole Potentiates Radiation Therapy in Triple-Negative Breast Cancer

Mebendazole Potentiates Radiation Therapy in Triple-Negative Breast Cancer

Inhibition of human immunodeficiency virus type 1 by niclosamide through mTORC1 inhibition

Integrating Genetic and Genomic Analyses of Combined Health Data Across Ecotypes to Improve Disease Resistance in Indigenous African Chickens

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