Sevoflurane modulates the cancer stem cell-like properties and mitochondrial membrane potential of glioma via Ca2+-dependent CaMKII/JNK cascade.
Life Sci
; 253: 117675, 2020 Jul 15.
Article
in En
| MEDLINE
| ID: mdl-32360621
ABSTRACT
AIMS:
Gliomas are responsible for the majority of deaths from primary brain tumours. Sevoflurane showed inhibition effects on the tumor progression in vitro. However, whether sevoflurane could affect the stemness of glioma stem cells (GSCs) and the potential molecular mechanism have not been well elucidated. MAINMETHODS:
Effects of sevoflurane on cell viability, proliferation and invasion ability of glioma cells as well as tumor growth in vivo were assessed. Sphere formation assay was performed to evaluate the effect of sevoflurane on the stemness of GSCs. Effects of sevoflurane on mitochondrial function was evaluated by intracellular/mitochondrial reactive oxygen species (ROS) level and mitochondrial membrane potential. Expression levels of proliferation-related proteins, stemness markers and proteins in CaMKII/JNK cascade were measured by Western blot. KEYFINDINGS:
Sevoflurane inhibited the viability, proliferation and invasion ability of glioma cells (U87MG and U373MG). Western blot showed that sevoflurane decreased the expression levels of proliferation and invasion-related proteins. Sphere formation ability of GSCs, expression levels of stemness markers and mitochondrial function were significantly suppressed by sevoflurane. Moreover, sevoflurane treatment significantly increased the Ca2+ concentration and stimulated phosphorylation of CaMKII, JNK and IRS1. Ca2+ chelator BAPTA-AM combined with sevoflurane synergistically inhibited colony forming ability and the expression levels of proliferation-related proteins and stemness markers. In addition, the in vivo study further confirmed that sevoflurane inhibited tumor growth via Ca2+-dependent CaMKII/JNK cascade.SIGNIFICANCE:
The present study demonstrated that sevoflurane inhibited glioma tumorigenesis and modulated the cancer stem cell-like properties and mitochondrial membrane potential via activation of Ca2+-dependent CaMKII/JNK cascade.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neoplastic Stem Cells
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MAP Kinase Kinase 4
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Membrane Potential, Mitochondrial
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Sevoflurane
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
Life Sci
Year:
2020
Document type:
Article