当前位置： SCI文献检索 > Cancer Cell International期刊下所有文献 > Melatonin enhances TNF-α-mediated cervical cancer HeLa cells death via suppressing CaMKII/Parkin/mitophagy axis.

Melatonin enhances TNF-α-mediated cervical cancer HeLa cells death via suppressing CaMKII/Parkin/mitophagy axis.

Abstract：

Background:Tumor necrosis factor-α (TNF-α) 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-α injury, with a particular attention to the mitochondrial homeostasis. Methods:HeLa cells were incubated with TNFα 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-α 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-α-mediated cancer death via repressing mitophagy. TNF-α treatment activated mitophagy via elevating Parkin expression and excessive mitophagy blocked mitochondrial apoptosis, ultimately alleviating the lethal action of TNF-α on HeLa cell. However, melatonin supplementation could prevent TNF-α-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-α-induced human cervical cancer HeLa cells mitochondrial apoptosis via inactivating the CaMKII/Parkin/mitophagy axis.

journal_name

Cancer Cell Int

journal_title

Cancer cell international

authors

Zhao Q,Wang W,Cui J

doi

10.1186/s12935-019-0777-2

subject

Has Abstract

pub_date

2019-03-14 00:00:00

pages

issn

1475-2867

pii

777

journal_volume

pub_type

杂志文章

在线工具

Melatonin enhances TNF-α-mediated cervical cancer HeLa cells death via suppressing CaMKII/Parkin/mitophagy axis.