Targeting Cancer Mitochondria by Inducing an Abnormal Mitochondrial Unfolded Protein Response Leads to Tumor Suppression

Wang, Baoxiao1; Chen, Wenjun1; Huang, Qiqi1; Chen, Ye2; Wang, Yajing1

2024

10.7150/ijms.95624

INTERNATIONAL JOURNAL OF MEDICAL SCIENCES   影响因子和分区

1449-1907

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.

nasopharyngeal carcinoma mitochondrial unfolded protein response mitochondria cisplatin oxidative stress

SCI

英语

其他

National Natural Science Foundation of China[82101227] ; Science and Technology Foundation of Guangzhou[2023A04J2091]

General & Internal Medicine

Medicine, General & Internal

WOS:001232019100016

IVYSPRING INT PUBL

Web of Science

1.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Otolaryngol Head & Neck Surg, Guangzhou, Peoples R China
2.Southern Univ Sci & Technol, Sch Med, Shenzhen, Guangdong, Peoples R China

Wang, Baoxiao,Chen, Wenjun,Huang, Qiqi,et al. Targeting Cancer Mitochondria by Inducing an Abnormal Mitochondrial Unfolded Protein Response Leads to Tumor Suppression[J]. INTERNATIONAL JOURNAL OF MEDICAL SCIENCES,2024,21(7).

Wang, Baoxiao,Chen, Wenjun,Huang, Qiqi,Chen, Ye,&Wang, Yajing.(2024).Targeting Cancer Mitochondria by Inducing an Abnormal Mitochondrial Unfolded Protein Response Leads to Tumor Suppression.INTERNATIONAL JOURNAL OF MEDICAL SCIENCES,21(7).

Wang, Baoxiao,et al."Targeting Cancer Mitochondria by Inducing an Abnormal Mitochondrial Unfolded Protein Response Leads to Tumor Suppression".INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 21.7(2024).