ArticleCell death & disease2022
Inhibitory role of proguanil on the growth of bladder cancer via enhancing EGFR degradation and inhibiting its downstream signaling pathway to induce autophagy.
Article in Cell death & disease, 2022. 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, 18 citations in OpenAlex.
- Repression of EGFR by new biguanide 4C potentiated ovarian cancer to PARP inhibitors through down-regulation of BRCA2 and Rad51.Cell death & disease · 2026Article
- SMK-002 inhibits the growth of bladder cancer cells and increases their sensitivity to OsimertinibThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- The ubiquitination-autophagy axis in cancer therapy resistance: mechanistic insights and therapeutic opportunities.Frontiers in pharmacology · 2025Review
- Design, Synthesis, Anti-Proliferative Effects, and Mechanistic Details of Fluorine-Containing Biguanide Derivatives with Various Carbon Rings.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Article
- Inhibition of Cyclin D1 by Novel Biguanide Derivative YB-004 Increases the Sensitivity of Bladder Cancer to Olaparib via Causing G0 / G1 Arrest.International journal of biological sciences · 2025Article
- Integrating computational and experimental chemical biology revealed variable anticancer activities of phosphodiesterase isoenzyme 5 inhibitors (PDE5i) in lung cancer.RSC medicinal chemistry · 2024Article
- Proguanil Suppresses Breast Tumor Growth In Vitro and In Vivo by Inducing Apoptosis via Mitochondrial Dysfunction.Cancers · 2024Article
- Deguelin Restores Paclitaxel Sensitivity in Paclitaxel-Resistant Ovarian Cancer Cells via Inhibition of the EGFR Signaling Pathway.Cancer management and research · 2024Article
- From Genes to Therapy: Pituitary Adenomas in the Era of Precision Medicine.Biomedicines · 2023Review
- SL-scan identifies synthetic lethal interactions in cancer using metabolic networks.Scientific reports · 2023Article
- Metformin-Loaded Chitosan Hydrogels Suppress Bladder Tumor Growth in an Orthotopic Mouse Model via Intravesical Administration.Molecules (Basel, Switzerland) · 2023Article
- Review
- Synergistic augmentation of osimertinib-induced autophagic death by proguanil or rapamycin in bladder cancer.MedComm · 2023Article
- The role of E3 ubiquitin ligases and deubiquitinases in bladder cancer development and immunotherapy.Frontiers in immunology · 2023Review
- Epidermal growth factor regulates autophagy activity and endocytosis of yak cumulus cells in a concentration-dependent manner.Frontiers in veterinary science · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A major reason for the high mortality of patients with bladder cancer (BC) is that chemotherapy and surgery are only effective for very limited patients. Thus, developing novel treatment options becomes an urgent need for improving clinical outcomes and the quality of life for BC patients. Here, we demonstrated that proguanil significantly inhibited the growth of BC in vitro and in vivo. Importantly, our results indicated that the sensitivity of BC cells to proguanil is positively correlated with the expression of epidermal growth factor receptor (EGFR). Mechanistically, proguanil specifically targeted EGFR and promoted EGFR binding to Caveolin-1, enhanced its endocytosis in a Clathrin-independent manner, and then recruited c-Cbl to promote EGFR ubiquitination and degradation through the lysosomal pathway. Further studies suggested that proguanil induced autophagy by destabilizing EGFR and inhibiting its downstream signaling pathway. Thus, this study reveals the novel mechanism of proguanil on anticancer activity and implies the potential benefits of this drug in the treatment of BC.
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