ArticleJournal of cancer research and clinical oncology2023
Repurposing of triamterene as a histone deacetylase inhibitor to overcome cisplatin resistance in lung cancer treatment.
Article in Journal of cancer research and clinical oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Current clinical applications and future developments of platinum-based anticancer drugs.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026Review
- Empagliflozin enhances cisplatin activity in chemo-resistant EJ138 bladder cancer cells: The importance of anti-diabetic medications in cancer treatment.Scientific reports · 2026Article
- Curcumin Derivative CU4c Exhibits HDAC-Inhibitory and Anticancer Activities Against Human Lung Cancer Cells In Vitro and in Mouse Xenograft Models.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Synergistic Anti-Cancer Activities of Curcumin Derivative CU17 Combined with Gemcitabine Against A549 Non-Small-Cell Lung Cancer Cells.Pharmaceutics · 2025Article
- USP5-dependent HDAC1 promotes cisplatin resistance and the malignant progression of non-small cell lung cancer by regulating RILP acetylation levels.Thoracic cancer · 2025Article
- In-depth analysis of immune cell landscapes reveals differences between lung adenocarcinoma and lung squamous cell carcinoma.Frontiers in oncology · 2024Article
- Circumvention of Gefitinib Resistance by Repurposing Flunarizine via Histone Deacetylase Inhibition.ACS pharmacology & translational science · 2023Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
purposeCisplatin is the core chemotherapeutic drug used for first-line treatment of advanced non-small cell lung cancer (NSCLC). However, drug resistance is severely hindering its clinical efficacy. This study investigated the circumvention of cisplatin resistance by repurposing non-oncology drugs with putative histone deacetylase (HDAC) inhibitory effect.
methodsA few clinically approved drugs were identified by a computational drug repurposing tool called "DRUGSURV" and evaluated for HDAC inhibition. Triamterene, originally indicated as a diuretic, was chosen for further investigation in pairs of parental and cisplatin-resistant NSCLC cell lines. Sulforhodamine B assay was used to evaluate cell proliferation. Western blot analysis was performed to examine histone acetylation. Flow cytometry was used to examine apoptosis and cell cycle effects. Chromatin immunoprecipitation was conducted to investigate the interaction of transcription factors to the promoter of genes regulating cisplatin uptake and cell cycle progression. The circumvention of cisplatin resistance by triamterene was further verified in a patient-derived tumor xenograft (PDX) from a cisplatin-refractory NSCLC patient.
resultsTriamterene was found to inhibit HDACs. It was shown to enhance cellular cisplatin accumulation and potentiate cisplatin-induced cell cycle arrest, DNA damage, and apoptosis. Mechanistically, triamterene was found to induce histone acetylation in chromatin, thereby reducing the association of HDAC1 but promoting the interaction of Sp1 with the gene promoter of hCTR1 and p21. Triamterene was further shown to potentiate the anti-cancer effect of cisplatin in cisplatin-resistant PDX in vivo.
conclusionThe findings advocate further clinical evaluation of the repurposing use of triamterene to overcome cisplatin resistance.
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