PMID- 28904818
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220330
IS  - 2058-7716 (Print)
IS  - 2058-7716 (Electronic)
IS  - 2058-7716 (Linking)
VI  - 3
DP  - 2017
TI  - NF-kappaB pathway link with ER stress-induced autophagy and apoptosis in cervical 
      tumor cells.
PG  - 17059
LID - 10.1038/cddiscovery.2017.59 [doi]
AB  - 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 1alpha, 
      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 IkappaBalpha protein and translocation 
      into the nucleus of NF-kappaB p65. Quinazolinediamine, an NF-kappaB 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-kappaB pathways controls the fate of cervical cancer cells. Careful evaluation 
      should be given to the addition of an NF-kappaB pathway inhibitor to treat cervical 
      cancer in combination with drugs that induce ER stress-mediated cell death.
FAU - Zhu, Xiaolan
AU  - Zhu X
AD  - Department of Human Anatomy, School of Basic Medical Sciences, Guangzhou Medical 
      University, Guangzhou, Guangdong 511436, People's Republic of China.
FAU - Huang, Li
AU  - Huang L
AD  - Department of Human Anatomy, School of Basic Medical Sciences, Guangzhou Medical 
      University, Guangzhou, Guangdong 511436, People's Republic of China.
FAU - Gong, Jie
AU  - Gong J
AD  - Department of Human Anatomy, School of Basic Medical Sciences, Guangzhou Medical 
      University, Guangzhou, Guangdong 511436, People's Republic of China.
FAU - Shi, Chun
AU  - Shi C
AD  - Department of Human Anatomy, School of Basic Medical Sciences, Guangzhou Medical 
      University, Guangzhou, Guangdong 511436, People's Republic of China.
FAU - Wang, Zhiming
AU  - Wang Z
AD  - Department of Human Anatomy, School of Basic Medical Sciences, Guangzhou Medical 
      University, Guangzhou, Guangdong 511436, People's Republic of China.
FAU - Ye, Bingkun
AU  - Ye B
AD  - Department of Human Anatomy, School of Basic Medical Sciences, Guangzhou Medical 
      University, Guangzhou, Guangdong 511436, People's Republic of China.
FAU - Xuan, Aiguo
AU  - Xuan A
AD  - Department of Human Anatomy, School of Basic Medical Sciences, Guangzhou Medical 
      University, Guangzhou, Guangdong 511436, People's Republic of China.
FAU - He, Xiaosong
AU  - He X
AD  - Department of Human Anatomy, School of Basic Medical Sciences, Guangzhou Medical 
      University, Guangzhou, Guangdong 511436, People's Republic of China.
FAU - Long, Dahong
AU  - Long D
AD  - Department of Human Anatomy, School of Basic Medical Sciences, Guangzhou Medical 
      University, Guangzhou, Guangdong 511436, People's Republic of China.
FAU - Zhu, Xiao
AU  - Zhu X
AD  - Guangdong Province Key Laboratory of Medical Molecular Diagnosis, Guangdong 
      Medical College, Zhanjiang/Dongguan, People's Republic of China.
FAU - Ma, Ningfang
AU  - Ma N
AD  - Key Laboratory of Protein Modification and Degradation, School of Basic Medical 
      Sciences, Affiliated Cancer Hospital and Institute of Guangzhou Medical 
      University, Guangzhou 511436, People's Republic of China.
FAU - Leng, Shuilong
AU  - Leng S
AD  - Department of Human Anatomy, School of Basic Medical Sciences, Guangzhou Medical 
      University, Guangzhou, Guangdong 511436, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20170911
PL  - United States
TA  - Cell Death Discov
JT  - Cell death discovery
JID - 101665035
PMC - PMC5592653
COIS- The authors declare no conflict of interest.
EDAT- 2017/09/15 06:00
MHDA- 2017/09/15 06:01
PMCR- 2017/09/11
CRDT- 2017/09/15 06:00
PHST- 2017/05/10 00:00 [received]
PHST- 2017/06/25 00:00 [revised]
PHST- 2017/06/30 00:00 [accepted]
PHST- 2017/09/15 06:00 [entrez]
PHST- 2017/09/15 06:00 [pubmed]
PHST- 2017/09/15 06:01 [medline]
PHST- 2017/09/11 00:00 [pmc-release]
AID - cddiscovery201759 [pii]
AID - 10.1038/cddiscovery.2017.59 [doi]
PST - epublish
SO  - Cell Death Discov. 2017 Sep 11;3:17059. doi: 10.1038/cddiscovery.2017.59. 
      eCollection 2017.