ArticlePLoS neglected tropical diseases2014
Profound activity of the anti-cancer drug bortezomib against Echinococcus multilocularis metacestodes identifies the proteasome as a novel drug target for cestodes.
Article in PLoS neglected tropical diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 60 citations in OpenAlex.
- Polarization of Hepatic Macrophages in Alveolar Echinococcosis and Its Role in Remodeling the Immune Microenvironment.Tropical medicine and infectious disease · 2026Review
- Progress on new drug treatments for hepatic echinococcosis.Frontiers in pharmacology · 2026Review
- Human Alveolar Echinococcosis-A Neglected Zoonotic Disease Requiring Urgent Attention.International journal of molecular sciences · 2025Review
- Efficacy and safety of pseudolaric acid B againstFrontiers in medicine · 2025Article
- Current status of drug therapy for alveolar echinococcosis.World journal of hepatology · 2024Review
- Enhancing the therapeutic potential of P29 protein-targeted monoclonal antibodies in the management of alveolar echinococcosis through CDC-mediated mechanisms.PLoS pathogens · 2024Article
- The proteasome as a drug target for treatment of parasitic diseases.Advances in parasitology · 2024Review
- Chemotherapy for the treatment of alveolar echinococcosis: Where are we?Parasite (Paris, France) · 2024Review
- Effect of sunitinib against Echinococcus multilocularis through inhibition of VEGFA-induced angiogenesis.Parasites & vectors · 2023Article
- 2-Deoxy-D-glucose and combined 2-Deoxy-D-glucose/albendazole exhibit therapeutic efficacy against Echinococcus granulosus protoscoleces and experimental alveolar echinococcosis.PLoS neglected tropical diseases · 2022Article
- Advances in the pharmacological treatment of hepatic alveolar echinococcosis: From laboratory to clinic.Frontiers in microbiology · 2022Review
- Microbial proteasomes as drug targets.PLoS pathogens · 2021Review
- In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis.Parasites & vectors · 2021Article
- In vivo and in vitro efficacy of crocin against Echinococcus multilocularis.Parasites & vectors · 2021Article
- Old drug repurposing for neglected disease: Pyronaridine as a promising candidate for the treatment of Echinococcus granulosus infections.EBioMedicine · 2020Article
- Glycogen Phosphorylase: A Drug Target of Amino Alcohols inFrontiers in microbiology · 2020Article
- In vitro and in vivo effects of 3-bromopyruvate against Echinococcus metacestodes.Veterinary research · 2019Article
- The importance of being parasiticidal… an update on drug development for the treatment of alveolar echinococcosis.Food and waterborne parasitology · 2019Article
- Effect of anacardic acid against echinococcosis through inhibition of VEGF-induced angiogenesis.Veterinary research · 2019Article
- Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets.PLoS neglected tropical diseases · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A library of 426 FDA-approved drugs was screened for in vitro activity against E. multilocularis metacestodes employing the phosphoglucose isomerase (PGI) assay. Initial screening at 20 µM revealed that 7 drugs induced considerable metacestode damage, and further dose-response studies revealed that bortezomib (BTZ), a proteasome inhibitor developed for the chemotherapy of myeloma, displayed high anti-metacestodal activity with an EC50 of 0.6 µM. BTZ treatment of E. multilocularis metacestodes led to an accumulation of ubiquinated proteins and unequivocally parasite death. In-gel zymography assays using E. multilocularis extracts demonstrated BTZ-mediated inhibition of protease activity in a band of approximately 23 kDa, the same size at which the proteasome subunit beta 5 of E. multilocularis could be detected by Western blot. Balb/c mice experimentally infected with E. multilocularis metacestodes were used to assess BTZ treatment, starting at 6 weeks post-infection by intraperitoneal injection of BTZ. This treatment led to reduced parasite weight, but to a degree that was not statistically significant, and it induced adverse effects such as diarrhea and neurological symptoms. In conclusion, the proteasome was identified as a drug target in E. multilocularis metacestodes that can be efficiently inhibited by BTZ in vitro. However, translation of these findings into in vivo efficacy requires further adjustments of treatment regimens using BTZ, or possibly other proteasome inhibitors.
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