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Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition
- Source :
- International Journal of Molecular Sciences; Volume 23; Issue 21; Pages: 13014
- Publication Year :
- 2022
- Publisher :
- MDPI AG, 2022.
-
Abstract
- Modulation of lipid metabolism is a well-established cancer hallmark, and SCD1 has been recognized as a key enzyme in promoting cancer cell growth, including in glioblastoma (GBM), the deadliest brain tumor and a paradigm of cancer resistance. The central goal of this work was to identify, by MS, the phospholipidome alterations resulting from the silencing of SCD1 in human GBM cells, in order to implement an innovative therapy to fight GBM cell resistance. With this purpose, RNAi technology was employed, and low serum-containing medium was used to mimic nutrient deficiency conditions, at which SCD1 is overexpressed. Besides the expected increase in the saturated to unsaturated fatty acid ratio in SCD1 silenced-GBM cells, a striking increase in polyunsaturated chains, particularly in phosphatidylethanolamine and cardiolipin species, was noticed and tentatively correlated with an increase in autophagy (evidenced by the increase in LC3BII/I ratio). The contribution of autophagy to mitigate the impact of SCD1 silencing on GBM cell viability and growth, whose modest inhibition could be correlated with the maintenance of energetically associated mitochondria, was evidenced by using autophagy inhibitors. In conclusion, SCD1 silencing could constitute an important tool to halt GBM resistance to the available treatments, especially when coupled with a mitochondria disrupter chemotherapeutic.
- Subjects :
- Cell Survival
Organic Chemistry
General Medicine
Catalysis
Computer Science Applications
Inorganic Chemistry
Autophagy
stearoyl CoA-desaturase 1 (SCD1)
glioblastoma
RNA interference technology
mass spectrometry
fatty acid and phospholipid composition
cell viability and proliferation
mitochondria respiratory activity
autophagy inhibition
Humans
Physical and Theoretical Chemistry
Glioblastoma
Molecular Biology
Stearoyl-CoA Desaturase
Phospholipids
Spectroscopy
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....a47afbe52edb158170b0ccf45bbc0a29
- Full Text :
- https://doi.org/10.3390/ijms232113014