ArticleThe Journal of biological chemistry2012
Impairment of the ubiquitin-proteasome pathway by methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl)carbamate leads to a potent cytotoxic effect in tumor cells: a novel antiproliferative agent with a potential therapeutic implication.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- A Systematic Review of the Impact of Benzimidazole-based Anthelmintics on Lung Cancer in Animal Models.Current drug safety · 2025Pooled it
- Fenbendazole Exhibits Antitumor Activity Against Cervical Cancer Through Dual Targeting of Cancer Cells and Cancer Stem Cells: Evidence from In Vitro and In Vivo Models.Molecules (Basel, Switzerland) · 2025Article
- Transcriptome analysis reveals the anticancer effects of fenbendazole on ovarian cancer: an in vitro and in vivo study.BMC cancer · 2024Article
- Anticancer Evaluation of Methoxy Poly(Ethylene Glycol)-International journal of nanomedicine · 2023Article
- Mebendazole Impedes the Proliferation and Migration of Pancreatic Cancer Cells through SK1 Inhibition Dependent Pathway.Molecules (Basel, Switzerland) · 2022Article
- Exceptional Repositioning of Dog Dewormer: Fenbendazole Fever.Current issues in molecular biology · 2022Review
- Review
- Anti-cancer effects of fenbendazole on 5-fluorouracil-resistant colorectal cancer cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- Transcriptional drug repositioning and cheminformatics approach for differentiation therapy of leukaemia cells.Scientific reports · 2021Article
- GRP78 in lung cancer.Journal of translational medicine · 2021Review
- Optimization and Pharmacokinetic Evaluation of Synergistic Fenbendazole and Rapamycin Co-Encapsulated in Methoxy Poly(Ethylene Glycol)-International journal of nanomedicine · 2021Article
- Potential and mechanism of mebendazole for treatment and maintenance of ovarian cancer.Gynecologic oncology · 2021Article
- Physicochemical, Pharmacokinetic, and Toxicity Evaluation of SoluplusPharmaceutics · 2020Article
- The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs.Immune network · 2020Review
- Similarities and differences in the biotransformation and transcriptomic responses of Caenorhabditis elegans and Haemonchus contortus to five different benzimidazole drugs.International journal for parasitology. Drugs and drug resistance · 2019Article
- Article
- Benzimidazoles Downregulate Mdm2 and MdmX and Activate p53 in MdmX Overexpressing Tumor Cells.Molecules (Basel, Switzerland) · 2019Article
- Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer cell death by modulating multiple cellular pathways.Scientific reports · 2018Article
- Gene co-expression network analysis identifies porcine genes associated with variation in metabolizing fenbendazole and flunixin meglumine in the liver.Scientific reports · 2017Article
- SRD5A2 gene expression inhibits cell migration and invasion in prostate cancer cell line via F-actin reorganization.Molecular and cellular biochemistry · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In recent years, there has been a great deal of interest in proteasome inhibitors as a novel class of anticancer drugs. We report that fenbendazole (FZ) (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl)carbamate) exhibits a potent growth-inhibitory activity against cancer cell lines but not normal cells. We show here, using fluorogenic substrates, that FZ treatment leads to the inhibition of proteasomal activity in the cells. Succinyl-Leu-Leu-Val-Tyr-methylcoumarinamide (MCA), benzyloxycarbonyl-Leu-Leu-Glu-7-amido-4-MCA, and t-butoxycarbonyl-Gln-Ala-Arg-7-amido-4-MCA fluorescent derivatives were used to assess chymotrypsin-like, post-glutamyl peptidyl-hydrolyzing, and trypsin-like protease activities, respectively. Non-small cell lung cancer cells transiently transfected with an expression plasmid encoding pd1EGFP and treated with FZ showed an accumulation of the green fluorescent protein in the cells due to an increase in its half-life. A number of apoptosis regulatory proteins that are normally degraded by the ubiquitin-proteasome pathway like cyclins, p53, and IκBα were found to be accumulated in FZ-treated cells. In addition, FZ induced distinct ER stress-associated genes like GRP78, GADD153, ATF3, IRE1α, and NOXA in these cells. Thus, treatment of human NSCLC cells with fenbendazole induced endoplasmic reticulum stress, reactive oxygen species production, decreased mitochondrial membrane potential, and cytochrome c release that eventually led to cancer cell death. This is the first report to demonstrate the inhibition of proteasome function and induction of endoplasmic reticulum stress/reactive oxygen species-dependent apoptosis in human lung cancer cell lines by fenbendazole, which may represent a new class of anticancer agents showing selective toxicity against cancer cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.