1. Targeting Cancer Mitochondria by Inducing an Abnormal Mitochondrial Unfolded Protein Response Leads to Tumor Suppression.
- Author
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Wang B, Chen W, Huang Q, Chen Y, and Wang Y
- Subjects
- Humans, Cell Line, Tumor, Membrane Potential, Mitochondrial drug effects, Nasopharyngeal Neoplasms pathology, Nasopharyngeal Neoplasms drug therapy, Nasopharyngeal Neoplasms metabolism, Nasopharyngeal Carcinoma pathology, Nasopharyngeal Carcinoma drug therapy, Nasopharyngeal Carcinoma metabolism, Nasopharyngeal Carcinoma genetics, Antineoplastic Agents pharmacology, Cell Survival drug effects, Unfolded Protein Response drug effects, Mitochondria metabolism, Mitochondria drug effects, Cisplatin pharmacology, Cisplatin therapeutic use, Apoptosis drug effects, Reactive Oxygen Species metabolism
- Abstract
The mitochondrial unfolded protein response (UPRmt) is a pivotal cellular mechanism that ensures mitochondrial homeostasis and cellular survival under stress conditions. This study investigates the role of UPRmt in modulating the response of nasopharyngeal carcinoma cells to cisplatin-induced stress. We report that the inhibition of UPRmt via AEB5F exacerbates cisplatin cytotoxicity, as evidenced by increased lactate dehydrogenase (LDH) release and apoptosis, characterized by a surge in TUNEL-positive cells. Conversely, the activation of UPRmt with oligomycin attenuates these effects, preserving cell viability and reducing apoptotic markers. Immunofluorescence assays reveal that UPRmt activation maintains mitochondrial membrane potential and ATP production in the presence of cisplatin, countering the rise in reactive oxygen species (ROS) and inhibiting caspase-9 activation. These findings suggest that UPRmt serves as a cytoprotective mechanism in cancer cells, mitigating cisplatin-induced mitochondrial dysfunction and apoptosis. The data underscore the therapeutic potential of modulating UPRmt to improve the efficacy and reduce the side effects of cisplatin chemotherapy. This study provides a foundation for future research on the exploitation of UPRmt in cancer treatment, with the aim of enhancing patient outcomes by leveraging the cellular stress response pathways., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
- Published
- 2024
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