PMID- 30923460
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230420
IS  - 1475-2867 (Print)
IS  - 1475-2867 (Electronic)
IS  - 1475-2867 (Linking)
VI  - 19
DP  - 2019
TI  - Melatonin enhances TNF-alpha-mediated cervical cancer HeLa cells death via 
      suppressing CaMKII/Parkin/mitophagy axis.
PG  - 58
LID - 10.1186/s12935-019-0777-2 [doi]
LID - 58
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) immunotherapy controls the 
      progression of human cervical cancer. Here, we explored the detailed molecular 
      mechanisms played by melatonin in human cervical cancer (HeLa cells) death in the 
      presence of TNF-alpha injury, with a particular attention to the mitochondrial 
      homeostasis. METHODS: HeLa cells were incubated with TNFalpha and then cell death was 
      determined via MTT assay, TUNEL staining, caspase ELISA assay and western 
      blotting. Mitochondrial function was detected via analyzing mitochondrial 
      membrane potential using JC-1 staining, mitochondrial oxidative stress using flow 
      cytometry and mitochondrial apoptosis using western blotting. RESULTS: Our data 
      exhibited that treatment with HeLa cells using melatonin in the presence of TNF-alpha 
      further triggered cancer cell cellular death. Molecular investigation 
      demonstrated that melatonin enhanced the caspase-9 mitochondrion death, repressed 
      mitochondrial potential, increased ROS production, augmented mPTP opening rate 
      and elevated cyt-c expression in the nucleus. Moreover, melatonin application 
      further suppressed mitochondrial ATP generation via reducing the expression of 
      mitochondrial respiratory complex. Mechanistically, melatonin augmented the 
      response of HeLa cells to TNF-alpha-mediated cancer death via repressing mitophagy. 
      TNF-alpha treatment activated mitophagy via elevating Parkin expression and excessive 
      mitophagy blocked mitochondrial apoptosis, ultimately alleviating the lethal 
      action of TNF-alpha on HeLa cell. However, melatonin supplementation could prevent 
      TNF-alpha-mediated mitophagy activation via inhibiting Parkin in a CaMKII-dependent 
      manner. Interestingly, reactivation of CaMKII abolished the melatonin-mediated 
      mitophagy arrest and HeLa cell death. CONCLUSIONS: Overall, our data highlight 
      that melatonin enhances TNF-alpha-induced human cervical cancer HeLa cells 
      mitochondrial apoptosis via inactivating the CaMKII/Parkin/mitophagy axis.
FAU - Zhao, Qinghe
AU  - Zhao Q
AD  - Department of Obstetrics and Gynecology, The Second Affiliated Hospital of 
      Zhengzhou University, No.2 Jinba Road, Zhengzhou, 450014 China. GRID: 
      grid.452842.d
FAU - Wang, Wuliang
AU  - Wang W
AD  - Department of Obstetrics and Gynecology, The Second Affiliated Hospital of 
      Zhengzhou University, No.2 Jinba Road, Zhengzhou, 450014 China. GRID: 
      grid.452842.d
FAU - Cui, Jinquan
AU  - Cui J
AD  - Department of Obstetrics and Gynecology, The Second Affiliated Hospital of 
      Zhengzhou University, No.2 Jinba Road, Zhengzhou, 450014 China. GRID: 
      grid.452842.d
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
DEP - 20190314
PL  - England
TA  - Cancer Cell Int
JT  - Cancer cell international
JID - 101139795
RIN - Cancer Cell Int. 2023 Apr 20;23(1):78. PMID: 37081507
PMC - PMC6419493
OTO - NOTNLM
OT  - CaMKII/Parkin pathways
OT  - HeLa cell
OT  - Melatonin
OT  - Mitochondria
OT  - TNF-alpha
COIS- The authors declare that they have no competing interests.
EDAT- 2019/03/30 06:00
MHDA- 2019/03/30 06:01
PMCR- 2019/03/14
CRDT- 2019/03/30 06:00
PHST- 2019/02/07 00:00 [received]
PHST- 2019/03/08 00:00 [accepted]
PHST- 2019/03/30 06:00 [entrez]
PHST- 2019/03/30 06:00 [pubmed]
PHST- 2019/03/30 06:01 [medline]
PHST- 2019/03/14 00:00 [pmc-release]
AID - 777 [pii]
AID - 10.1186/s12935-019-0777-2 [doi]
PST - epublish
SO  - Cancer Cell Int. 2019 Mar 14;19:58. doi: 10.1186/s12935-019-0777-2. eCollection 
      2019.