학술논문
Fatty Acid Synthesis and Degradation Interplay to Regulate the Oxidative Stress in Cancer Cells.
Document Type
Academic Journal
Author
Mikalayeva V; Institute of Cardiology, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania. Valeryia.Mikalayeva@lsmuni.lt.; Ceslevičienė I; Institute of Cardiology, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania. Ieva.Cesleviciene@lsmuni.lt.; Sarapinienė I; Institute of Cardiology, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania. Ieva.Sarapiniene@lsmuni.lt.; Žvikas V; Institute of Pharmaceutical Technologies, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania. Vaidotas.Zvikas@lsmuni.lt.; Skeberdis VA; Institute of Cardiology, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania. Arvydas.Skeberdis@lsmuni.lt.; Jakštas V; Institute of Pharmaceutical Technologies, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania. Valdas.Jakstas@lsmuni.lt.; Bordel S; Institute of Cardiology, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania. Sergio.Bordel@lsmuni.lt.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
Subject
Language
English
Abstract
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 13 C-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.