Resiniferatoxin induces death of bladder cancer cells associated with mitochondrial dysfunction and reduces tumor growth in a xenograft mouse model.
Bladder cancer (BC) is the fifth most common non-cutaneous malignancy and the most common form of BC in Western countries is transitional cell carcinoma. Resiniferatoxin (RTX) has found therapeutic usefulness for the treatment of bladder dysfunction but no data are available on its use as chemotherapeutic agent. The aim of this work is to evaluate the use of RTX as new anti-cancer drug in BC therapy. The effects of RTX on cell viability and cell death were evaluated on T24 and 5637 BC cell lines by MTT assay, cell cycle analysis, Annexin-V/PI staining and agarose gel electrophoresis of DNA. Mitochondrial depolarization and ROS production were assessed by flow cytometry. ADP/ATP ratio was measured by bioluminescence and caspase 3 cleavage by Western blot. For in vivo experiments, athymic nude mice, xenografted with T24 cells, received subcutaneous administrations of RTX. Tumor volumes were measured and immunohistochemistry was performed on tumor sections. Our data demonstrated that RTX influences cell cycle and induces necrotic cell death of BC cells by altering mitochondrial function, leading to depolarization, increase in ADP/ATP ratio and ROS production. Moreover, RTX is able to reduce tumor growth in a xenograft mouse model. Overall, we demonstrated that RTX induces necrotic cell death of BC cells and reduces tumor growth in a xenograft mouse model of BC, suggesting RTX as a new potential anti-cancer drug in BC chemotherapy.
['Farfariello|Valerio|V|', 'Liberati|Sonia|S|', 'Morelli|Maria Beatrice|MB|', 'Tomassoni|Daniele|D|', 'Santoni|Matteo|M|', 'Nabissi|Massimo|M|', 'Giannantoni|Antonella|A|', 'Santoni|Giorgio|G|', 'Amantini|Consuelo|C|']
D000244:Adenosine Diphosphate D000255:Adenosine Triphosphate D000818:Animals D000970:Antineoplastic Agents D002295:Carcinoma, Transitional Cell D059447:Cell Cycle Checkpoints D045744:Cell Line, Tumor D004224:Diterpenes D006706:Homeostasis D006801:Humans D008297:Male D053078:Membrane Potential, Mitochondrial D051379:Mice D008819:Mice, Nude D008928:Mitochondria D009336:Necrosis D010084:Oxidation-Reduction D017382:Reactive Oxygen Species D050916:TRPV Cation Channels D001749:Urinary Bladder Neoplasms D023041:Xenograft Model Antitumor Assays
Resiniferatoxin Bladder cancer Xenograft Mitochondria Necrosis