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Träfflista för sökning "WFRF:(Enriquez J. E.) srt2:(2008-2009)"

Sökning: WFRF:(Enriquez J. E.) > (2008-2009)

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  • Dong, Lan-Feng, et al. (författare)
  • Suppression of Tumor Growth In vivo by the Mitocan alpha-tocopheryl Succinate Requires Respiratory Complex II
  • 2009
  • Ingår i: CLINICAL CANCER RESEARCH. - 1078-0432. ; 15:5, s. 1593-1600
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Vitamin E analogues are potent novel anticancer drugs. The purpose of this study was to elucidate the cellular target by which these agents, represented by alpha-tocopoheryl succinate (alpha-TOS), suppress tumors in vivo, with the focus on the mitochondrial complex II (CII). Experimental Design: Chinese hamster lung fibroblasts with functional, dysfunctional, and reconstituted CII were transformed using H-Ras. The cells were then used to form xenografts in immunocompromized mice, and response of the cells and the tumors to alpha-TOS was studied. Results: The CII-functional and CII-reconstituted cells, unlike their CII-dysfunctional counterparts, responded to alpha-TOS by reactive oxygen species generation and apoptosis execution. Tumors derived from these cell lines reciprocated their responses to alpha-TOS. Thus, growth of CII-functional and CII-reconstituted tumors was strongly suppressed by the agent, and this was accompanied by high level of apoptosis induction in the tumor cells. On the other hand, alpha-TOS did not inhibit the CII-dysfuntional tumors. Conclusions: We document in this report a novel paradigm, according to which the mitochondrial CII, which rarely mutates in human neoplasias, is a plausible target for anticancer drugs from the group of vitamin E analogues, providing support for their testing in clinical trials.
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