Affinity of vitamin E analogues for the ubiquinone complex II site correlates with their toxicity to cancer cells

0369496 - BTÚ 2012 RIV US eng J - Journal Article
Neužil, Jiří - Černý, Jiří - Dyason, J.C. - Dong, L.-F. - Ralph, S.J.
Affinity of vitamin E analogues for the ubiquinone complex II site correlates with their toxicity to cancer cells.
Molecular Nutrition & Food Research. Roč. 55, č. 10 (2011), s. 1543-1551. ISSN 1613-4125. E-ISSN 1613-4133
Institutional research plan: CEZ:AV0Z50520701
Keywords : Vitamin E analogues * mitochondrial complex II * modelling
Subject RIV: CE - Biochemistry
Impact factor: 4.301, year: 2011

Vitamin E (VE) analogues, epitomised by the prototypic alpha-tocopheryl succinate (alpha-TOS), are potent anti-cancer agents. alpha-TOS has recently been shown to trigger apoptosis by targeting the ubiquinone (UbQ) binding site(s) of the mitochondrial complex II (CII) and to cause excessive production of reactive oxygen species. We have modelled, using two approaches, a range of VE analogues into the proximal UbQ (Q(P)) binding site of CII. This study reveals that in both cases, the calculated interaction energies of individual VE analogues correlate (R(2) value >0.8) with their toxicity to cancer cells. These data further support the UbQ site(s) of CII as an important target determining the anti-cancer activity of VE analogues as well as other emerging anti-cancer drugs.
Permanent Link: http://hdl.handle.net/11104/0203545