NF-κB pathway link with ER stress-induced autophagy and apoptosis in cervical tumor cells
| Autor: | Zhiming Wang, Xiaosong He, Bingkun Ye, Xiaolan Zhu, Aiguo Xuan, Ningfang Ma, Shuilong Leng, Xiao Zhu, Li Huang, Chun Shi, Dahong Long, Jie Gong |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Programmed cell death Thapsigargin biology Endoplasmic reticulum Immunology Autophagy Cell Biology Tunicamycin biology.organism_classification HeLa 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry Apoptosis 030220 oncology & carcinogenesis Cancer research Unfolded protein response |
| Zdroj: | Cell Death Discovery. 3 |
| ISSN: | 2058-7716 |
| DOI: | 10.1038/cddiscovery.2017.59 |
| Popis: | Targeting endoplasmic reticulum (ER) stress is being investigated for its anticancer effect in various cancers, including cervical cancer. However, the molecular pathways whereby ER stress mediates cell death remain to be fully elucidated. In this study, we confirmed that ER stress triggered by compounds such as brefeldin A (BFA), tunicamycin (TM), and thapsigargin (TG) leads to the induction of the unfolded protein response (UPR) in cervical cancer cell lines, which is characterized by elevated levels of inositol-requiring kinase 1α, glucose-regulated protein-78, and C/EBP homologous protein, and swelling of the ER observed by transmission electron microscope (TEM). We found that BFA significantly increased autophagy in tumor cells and induced TC-1 tumor cell death in a dose-dependent manner. BFA increased punctate staining of LC3 and the number of autophagosomes observed by TEM in TC-1 and HeLa cells. The autophagic flux was also assessed. Bafilomycin, which blocked degradation of LC3 in lysosomes, caused both LC3I and LC3II accumulation. BFA initiated apoptosis of TC-1 tumor cells through activation of the caspase-12/caspase-3 pathway. At the same time, BFA enhanced the phosphorylation of IκBα protein and translocation into the nucleus of NF-κB p65. Quinazolinediamine, an NF-κB inhibitor, attenuated both autophagy and apoptosis induced by BFA; meanwhile, it partly enhances survival of cervical cancer cells following BFA treatment. In conclusion, our results indicate that the cross-talk between ER stress, autophagy, apoptosis, and the NF-κB pathways controls the fate of cervical cancer cells. Careful evaluation should be given to the addition of an NF-κB pathway inhibitor to treat cervical cancer in combination with drugs that induce ER stress-mediated cell death. |
| Databáze: | OpenAIRE |
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