ArticleDrug design, development and therapy2020
Leflunomide Inhibits Proliferation and Induces Apoptosis via Suppressing Autophagy and PI3K/Akt Signaling Pathway in Human Bladder Cancer Cells.
Article in Drug design, development and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- Role of autophagy in tumorigenesis and drug resistance: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Highlighting the Therapeutic Potential of an Underexplored Target: Human Dihydroorotate Dehydrogenase in Cancer, Rheumatoid Arthritis and Sclerosis.Current topics in medicinal chemistry · 2026Review
- Transcriptomic analysis of the anti-tumor effects of leflunomide in prolactinoma.Scientific reports · 2025Article
- RET Inhibitor SPP86 Triggers Apoptosis and Activates the DNA Damage Response Through the Suppression of Autophagy and the PI3K/AKT Signaling Pathway in Melanoma Cells.Drug design, development and therapy · 2025Article
- Recent Progress of Glutathione Peroxidase 4 Inhibitors in Cancer Therapy.Mini reviews in medicinal chemistry · 2025Review
- Mechanisms of S-phase arrest and mitochondrial dysfunction in complex III by DHODH inhibitors in tumorigenic TNBC cells.Histochemistry and cell biology · 2024Article
- Teriflunomide/leflunomide synergize with chemotherapeutics by decreasing mitochondrial fragmentation via DRP1 in SCLC.iScience · 2024Article
- Leflunomide Treatment Does Not Protect Neural Cells following Oxygen-Glucose Deprivation (OGD) In Vitro.Cells · 2024Article
- Construction and validation of a cuproptosis-related lncRNA prognosis signature in bladder carcinoma.Journal of cancer research and clinical oncology · 2023Article
- PRRX1/FOXM1 reduces gemcitabin-induced cytotoxicity by regulating autophagy in bladder cancer.Translational andrology and urology · 2022Article
- Synthesis of novel isoxazole-carboxamide derivatives as promising agents for melanoma and targeted nano-emulgel conjugate for improved cellular permeability.BMC chemistry · 2022Article
- UBE2T-mediated Akt ubiquitination and Akt/β-catenin activation promotes hepatocellular carcinoma development by increasing pyrimidine metabolism.Cell death & disease · 2022Article
- Cell-Based Double-Screening Method to Identify a Reliable Candidate for Osteogenesis-Targeting Compounds.Biomedicines · 2022Article
- The Mitochondria-Independent Cytotoxic Effect of Leflunomide on RPMI-8226 Multiple Myeloma Cell Line.Molecules (Basel, Switzerland) · 2021Article
- Leflunomide an immunomodulator with antineoplastic and antiviral potentials but drug-induced liver injury: A comprehensive review.International immunopharmacology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionBladder cancer is a lethal human malignancy. Currently, treatment for bladder cancer is limited. The anti-tumor effects of leflunomide have attracted much more concern in multiple human cancers. MATERIALS AND
methodsThis study evaluated the anti-tumor effects of leflunomide on cell viability, colony formation, apoptosis, and cell cycle in two human bladder carcinoma cell lines, 5637 and T24. Meanwhile, the underlying mechanism including PI3K/Akt signaling pathway and autophagy modulation was also identified.
resultsLeflunomide markedly inhibited the growth of both bladder cancer cell lines and induced apoptosis and cell cycle arrest in S phase. The phosphorylation levels of Akt and P70S6K in both cell lines were significantly down-regulated with leflunomide treatment. Furthermore, the deceased formation of autophagosomes and the accumulation of LC3II and P62 suggested the blockade of autophagy by leflunomide. Modulation of autophagy with rapamycin and chloroquine markedly attenuated and enhanced the cytostatic effects of leflunomide, respectively.
conclusionLeflunomide significantly reduced the cell viability of bladder cancer cells via inducing apoptosis and cell cycle arrest and suppressing the PI3K/Akt signaling pathway. In addition, the blockade of autophagy was observed, and autophagy inhibition enhanced leflunomide-mediating anti-tumor effects. Our data presented here offer novel ideas for comprehensive therapeutic regimes on bladder cancer.
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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.