Sobotka 2014 Abstract IOC95
|Sobotka O (2014) Effect of α-Tocopheryl succinate on Complex II. Mitochondr Physiol Network 19.10|
α-Tocopheryl succinate (TOS) is a redox-silent analogue of vitamin E with specific anti-tumorous effects. According to some studies, TOS suppresses cell growth and induces apoptosis in cancer cells [1-3]. The inhibitory effect on transformed cells is related to an increase in reactive oxygen species (ROS) production possibly via inhibition of respiratory complex II - specifically mitochondrial flavoprotein-dependent enzymes succinate dehydrogenase (SDH) and glycerol-3-phosphate dehydrogenase (mGPDH) [1-4]. On the molecular level the effect of TOS is explained by interaction of TOS with the proximal and distal CoQ-binding sites of complex II . However such effect was not found in non-cancer cells [1, 3]. The aim of our study was to assess the inhibitory action of TOS on complex II in rat heart and liver homogenate and mitochondria. The maximum respiratory capacity of complex II induced by addition of succinate, cytochrome c and ADP was measured using the high resolution respirometry (HRR) Oroboros 2K. We evaluated the TOS inhibitory action on complex II respiration during concentration increase. The strong inhibitory effect of TOS on complex II respiration was found at the concentration range between 150-500 μM. Our results showed that both liver and heart mitochondria were more sensitive to TOS inhibitory action in comparison to homogenate. Our study using HRR method showed a TOS inhibitory action on complex II activity. Strong inhibitory effect was detected on heart and liver mitochondria as well as on the homogenate. Lower sensitivity of liver homogenate compared to mitochondria may be the result of the presence of cytosolic esterases which split the molecule of TOS to α-tocopherol and succinate  or due to binding of TOS to cytosolic membrane structures.
1. Angulo-Molina, A., et al., The Role of Alpha Tocopheryl Succinate (alpha-TOS) as a Potential Anticancer Agent. Nutr Cancer, 2013.
2. Zhao, Y., J. Neuzil, and K. Wu, Vitamin E analogues as mitochondria-targeting compounds: from the bench to the bedside? Mol Nutr Food Res, 2009. 53(1): p. 129-39.
3. Neuzil, J., et al., Molecular mechanism of 'mitocan'-induced apoptosis in cancer cells epitomizes the multiple roles of reactive oxygen species and Bcl-2 family proteins. FEBS Lett, 2006. 580(22): p. 5125-9. 4. Rauchova, H., M. Vokurkova, and Z. Drahota, Inhibition of mitochondrial glycerol-3-phosphate dehydrogenase by alpha-tocopheryl succinate. Int J Biochem Cell Biol, 2014. 53: p. 409-13.
Labels: MiParea: Respiration, Pharmacology;toxicology
Stress:Oxidative stress;RONS Organism: Rat Tissue;cell: Heart, Liver Preparation: Homogenate, Isolated mitochondria Enzyme: Complex II;succinate dehydrogenase
Coupling state: OXPHOS Pathway: S HRR: Oxygraph-2k