ArticleCancers2021
Repurposing Niclosamide for Targeting Pancreatic Cancer by Inhibiting Hh/Gli Non-Canonical Axis of Gsk3β.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Niclosamide as a Promising Therapeutic Player in Human Cancer and Other Diseases.International journal of molecular sciences · 2022Pooled it
- An Open Label, Cross-Over Phase 1 Study to Determine the Safety, Tolerability and Pharmacokinetics of Multiple Oral Doses of Niclosamide Under Fed and Fasted Conditions in Healthy Volunteers.Journal of clinical medicine · 2026Article
- Targeting Androgen Receptor as a Novel Radiosensitizing Therapy to Improve Long-Term Survival and Anti-tumor Immunity in Glioblastoma via TGF-β/Smad3 Axis Reprogramming.Research square · 2026Article
- Niclosamide nanoparticles enhance pancreatic cancer sensitivity to gemcitabine via HIF-1α inhibition.iScience · 2025Article
- Translational potential of safe-by-design nanoengineered niclosamide in viral and cancer therapy.Materials today. Bio · 2025Article
- Cholesterol metabolism: molecular mechanisms, biological functions, diseases, and therapeutic targets.Molecular biomedicine · 2025Review
- Role of S100 family proteins in colorectal cancer (CRC): an overview of their potential function as new biomarkers and therapeutic agents.Expert reviews in molecular medicine · 2025Review
- Oncogenic potential of truncated-Gli3 via the Gsk3β/Gli3/AR-V7 axis in castration-resistant prostate cancer.Oncogene · 2025Article
- Niclosamide-Loaded Polyanhydride Nanoparticles to Combat Gemcitabine Resistance in Pancreatic Cancer.Regenerative engineering and translational medicine · 2025Article
- Pyrvinium Pamoate Alone and With Gemcitabine Exhibits Anti-Pancreatic Cancer Activity in 2D and 3D Cell Culture Models.Journal of cellular and molecular medicine · 2024Article
- Optimizing Niclosamide for Cancer Therapy: Improving Bioavailability via Structural Modification and Nanotechnology.Cancers · 2024Review
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- New Salicylanilide Derivatives and Their Peptide Conjugates as Anticancer Compounds: Synthesis, Characterization, andACS omega · 2024Article
- Combination therapy of niclosamide with gemcitabine inhibited cell proliferation and apoptosis via Wnt/β-catenin/c-Myc signaling pathway by inducing β-catenin ubiquitination in pancreatic cancer.Cancer biology & therapy · 2023Article
- SAR study of niclosamide derivatives for neuroprotective function in SH-SY5Y neuroblastoma.Bioorganic & medicinal chemistry letters · 2023Article
- Anthelmintic Drugs as Emerging Immune Modulators in Cancer.International journal of molecular sciences · 2023Review
- Article
- Exploiting the molecular subtypes and genetic landscape in pancreatic cancer: the quest to find effective drugs.Frontiers in genetics · 2023Review
- Preparation of PLGA microspheres loaded with niclosamide via microfluidic technology and their inhibition of Caco-2 cell activityFrontiers in chemistry · 2023Article
- Glycogen Synthase Kinase 3β: A True Foe in Pancreatic Cancer.International journal of molecular sciences · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Niclosamide (Nic), an FDA-approved anthelmintic drug, is reported to have anti-cancer efficacy and is being assessed in clinical trials for various solid tumors. Based on its ability to target multiple signaling pathways, in the present study, we evaluated the therapeutic efficacy of Nic on pancreatic cancer (PC) in vitro. We observed an anti-cancerous effect of this drug as shown by the G0/G1 phase cell cycle arrest, inhibition of PC cell viability, colony formation, and migration. Our results revealed the involvement of mitochondrial stress and mTORC1-dependent autophagy as the predominant players of Nic-induced PC cell death. Significant reduction of Nic-induced reactive oxygen species (ROS) and cell death in the presence of a selective autophagy inhibitor spautin-1 demonstrated autophagy as a major contributor to Nic-mediated cell death. Mechanistically, Nic inhibited the interaction between BCL2 and Beclin-1 that supported the crosstalk of autophagy and apoptosis. Further, Nic treatment resulted in Gsk3β inactivation by phosphorylating its Ser-9 residue leading to upregulation of Sufu and Gli3, thereby negatively impacting hedgehog signaling and cell survival. Nic induced autophagic cell death, and p-Gsk3b mediated Sufu/Gli3 cascade was further confirmed by Gsk3β activator, LY-294002, by rescuing inactivation of Hh signaling upon Nic treatment. These results suggested the involvement of a non-canonical mechanism of Hh signaling, where p-Gsk3β acts as a negative regulator of Hh/Gli1 cascade and a positive regulator of autophagy-mediated cell death. Overall, this study established the therapeutic efficacy of Nic for PC by targeting p-Gsk3β mediated non-canonical Hh signaling and promoting mTORC1-dependent autophagy and cell death.
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.