Fatty Acid Synthesis and Degradation Interplay to Regulate the Oxidative Stress in Cancer Cells
- Resource Type
- Authors
- Ieva Ceslevičienė; Valdas Jakštas; Valeryia Mikalayeva; Ieva Sarapinienė; Sergio Bordel; Vaidotas Žvikas; Vytenis Arvydas Skeberdis
- Source
- International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 20, Iss 6, p 1348 (2019)
Volume 20
Issue 6
International journal of molecular sciences, Basel : MDPI, 2019, vol. 20, no. 6, 1348, p. 1-12
- Subject
- Breast Neoplasms
Mitochondrion
Fatty acid degradation
Breast neoplasms
metabolism
Cell line, tumor
Cell proliferation
Fatty acids
Oxidative stress
Catalysis
Article
Inorganic Chemistry
lcsh:Chemistry
lipids
chemistry.chemical_compound
618.19-006.6 [udc]
Cell Line, Tumor
medicine
Staurosporine
Humans
cancer
Physical and Theoretical Chemistry
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
Fatty acid synthesis
Membrane Potential, Mitochondrial
Carbon Isotopes
Chemistry
Organic Chemistry
digestive, oral, and skin physiology
Fatty Acids
Lipid metabolism
General Medicine
Metabolic Flux Analysis
Computer Science Applications
Glutamine
Cytosol
Oxidative Stress
Biochemistry
lcsh:Biology (General)
lcsh:QD1-999
Cancer cell
Female
Fatty Acid Synthases
Oxidation-Reduction
medicine.drug
- Language
- ISSN
- 1422-0067
Both cytosolic fatty acid synthesis (FAS) and mitochondrial fatty acid oxidation (FAO) have been shown to play a role in the survival and proliferation of cancer cells. This study aimed to confirm experimentally whether FAS and FAO coexist in breast cancer cells (BCC). By feeding cells with 13C-labeled glutamine and measuring labeling patterns of TCA intermediates, it was possible to show that part of the cytosolic acetyl-CoA used in lipid synthesis is also fed back into the mitochondrion via fatty acid degradation. This results in the transfer of reductive potential from the cytosol (in the form of NADPH) to the mitochondrion (in the form of NADH and FADH2). The hypothesized mechanism was further confirmed by blocking FAS and FAO with siRNAs. Exposure to staurosporine (which induces ROS production) resulted in the disruption of simultaneous FAS and FAO, which could be explained by NADPH depletion.