| pubmed-article:18372923 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18372923 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
| pubmed-article:18372923 | lifeskim:mentions | umls-concept:C0205145 | lld:lifeskim |
| pubmed-article:18372923 | lifeskim:mentions | umls-concept:C0521451 | lld:lifeskim |
| pubmed-article:18372923 | lifeskim:mentions | umls-concept:C0220918 | lld:lifeskim |
| pubmed-article:18372923 | lifeskim:mentions | umls-concept:C0599894 | lld:lifeskim |
| pubmed-article:18372923 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:18372923 | lifeskim:mentions | umls-concept:C1312550 | lld:lifeskim |
| pubmed-article:18372923 | pubmed:issue | 31 | lld:pubmed |
| pubmed-article:18372923 | pubmed:dateCreated | 2008-7-17 | lld:pubmed |
| pubmed-article:18372923 | pubmed:abstractText | Alpha-tocopheryl succinate (alpha-TOS) is a selective inducer of apoptosis in cancer cells, which involves the accumulation of reactive oxygen species (ROS). The molecular target of alpha-TOS has not been identified. Here, we show that alpha-TOS inhibits succinate dehydrogenase (SDH) activity of complex II (CII) by interacting with the proximal and distal ubiquinone (UbQ)-binding site (Q(P) and Q(D), respectively). This is based on biochemical analyses and molecular modelling, revealing similar or stronger interaction energy of alpha-TOS compared to that of UbQ for the Q(P) and Q(D) sites, respectively. CybL-mutant cells with dysfunctional CII failed to accumulate ROS and underwent apoptosis in the presence of alpha-TOS. Similar resistance was observed when CybL was knocked down with siRNA. Reconstitution of functional CII rendered CybL-mutant cells susceptible to alpha-TOS. We propose that alpha-TOS displaces UbQ in CII causing electrons generated by SDH to recombine with molecular oxygen to yield ROS. Our data highlight CII, a known tumour suppressor, as a novel target for cancer therapy. | lld:pubmed |
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| pubmed-article:18372923 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:18372923 | pubmed:citationSubset | IM | lld:pubmed |
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