Bardoxolone-methyl inhibits migration and metabolism in MCF7 cells

• Published in: Free radical research 2017-02, Vol.51 (2), p.211-221
• Main Authors: Refaat, Alaa, Pararasa, Chathyan, Arif, Muhammed, Brown, James E. P., Carmichael, Amtul, Ali, Sameh S., Sakurai, Hiroaki, Griffiths, Helen R.
• Format: Article
• Language: English
• Subjects: Antioxidants - metabolism; Apoptosis - drug effects; Blotting, Western; Breast cancer; Cell Movement - drug effects; Cell Proliferation - drug effects; glutathione; Glutathione - metabolism; glycolysis; Humans; MCF-7 Cells; mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Oleanolic Acid - analogs & derivatives; Oleanolic Acid - pharmacology; Oxidative Stress - drug effects; palmitate; reactive oxygen species; Reactive Oxygen Species - metabolism; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Signal Transduction - drug effects
• ISSN: 1071-5762; 1029-2470
• DOI: 10.1080/10715762.2017.1295452

Bardoxolone-methyl (BAR) is reported to have anti-inflammatory, anti-proliferative and anti-fibrotic effects. BAR activates Nrf2 and may ameliorate oxidative stress through induction of antioxidant genes. However, off-target effects, probably concentration and NFkB-dependent, have limited the clinical use of BAR. Nrf2 regulates expression of antioxidant and mitochondrial genes and has been proposed as a target for both obesity and breast cancer. Therefore, we explored whether BAR can alter migration and proliferation in the MCF7 cell line and whether metabolic function is affected by BAR. Incubation with BAR caused a time-dependent migratory inhibition and an associated decrease in mitochondrial respiration. Both migratory and mitochondrial inhibition by BAR were further enhanced in the presence of fatty acids. In addition to the activation of Nrf2, BAR altered the expression of target mRNA GCLC and UCP1. After 24 h, BAR inhibited both glycolytic capacity, reserve (p