ArticleCell death & disease2017
Thioridazine enhances sensitivity to carboplatin in human head and neck cancer cells through downregulation of c-FLIP and Mcl-1 expression.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Review
- Phenothiazine Derivatives and Their Impact on the Apoptosis Processes: A Review.Journal of applied toxicology : JAT · 2026Review
- Revealing New Prospects: Antipsychotic Drugs Induces Anti-tumor Effects against Gastric Cancer through Inducing Apoptosis.Current cancer drug targets · 2025Article
- Butein inhibits oral squamous cell carcinoma growth via promoting MCL-1 ubiquitination.Journal of Cancer · 2024Article
- Targeting Prostate Cancer, the 'Tousled Way'.International journal of molecular sciences · 2023Review
- The Therapeutic Potential of Carnosine as an Antidote against Drug-Induced Cardiotoxicity and Neurotoxicity: Focus on Nrf2 Pathway.Molecules (Basel, Switzerland) · 2022Review
- Myeloid cell leukemia-1 expression in cancers of the oral cavity: a scoping review.Cancer cell international · 2022Article
- The Mechanisms of Current Platinum Anticancer Drug Resistance in the Glioma.Current pharmaceutical design · 2022Review
- Bayesian hierarchical lasso Cox model: A 9-gene prognostic signature for overall survival in gastric cancer in an Asian population.PloS one · 2022Article
- Repurposing Antipsychotics for Cancer Treatment.Biomedicines · 2021Review
- EF24 exerts cytotoxicity against NSCLC via inducing ROS accumulation.Cancer cell international · 2021Article
- Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas.International journal of molecular sciences · 2021Review
- Article
- Pharmacological targeting of c-FLIPScientific reports · 2020Article
- Thioridazine requires calcium influx to induce MLL-AF6-rearranged AML cell death.Blood advances · 2020Article
- ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer.Oxidative medicine and cellular longevity · 2020Review
- Targeting the TLK1/NEK1 DDR axis with Thioridazine suppresses outgrowth of androgen independent prostate tumors.International journal of cancer · 2019Article
- Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis.International journal of molecular sciences · 2019Review
- Clinical update on head and neck cancer: molecular biology and ongoing challenges.Cell death & disease · 2019Review
- Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Carboplatin is a less toxic analog of cisplatin, but carboplatin also has side effects, including bone marrow suppression. Therefore, to improve the capacity of the anticancer activity of carboplatin, we investigated whether combined treatment with carboplatin and thioridazine, which has antipsychotic and anticancer activities, has a synergistic effect on apoptosis. Combined treatment with carboplatin and thioridazine markedly induced caspase-mediated apoptosis in head and neck squamous cell carcinoma (AMC-HN4) cells. Combined treatment with carboplatin and thioridazine induced downregulation of Mcl-1 and c-FLIP expression. Ectopic expression of Mcl-1 and c-FLIP inhibited carboplatin plus thioridazine-induced apoptosis. We found that augmentation of proteasome activity had a critical role in downregulation of Mcl-1 and c-FLIP expression at the post-translational level in carboplatin plus thioridazine-treated cells. Furthermore, carboplatin plus thioridazine induced upregulation of the expression of proteasome subunit alpha 5 (PSMA5) through mitochondrial reactive oxygen species (ROS)-dependent nuclear factor E2-related factor 2 (Nrf2) activation. In addition, combined treatment with carboplatin and thioridazine markedly induced apoptosis in human breast carcinoma (MDA-MB231) and glioma (U87MG) cells, but not in human normal mesangial cells and normal human umbilical vein cells (EA.hy926). Collectively, our study demonstrates that combined treatment with carboplatin and thioridazine induces apoptosis through proteasomal degradation of Mcl-1 and c-FLIP by upregulation of Nrf2-dependent PSMA5 expression.
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Registered trials
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