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Suppression of Tumor Growth In vivo by the Mitocan alpha-tocopheryl Succinate Requires Respiratory Complex II
Griffith University.
Griffith University.
Griffith University.
Griffith University.
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2009 (English)In: CLINICAL CANCER RESEARCH, ISSN 1078-0432 , Vol. 15, no 5, 1593-1600 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 15, no 5, 1593-1600 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-17382DOI: 10.1158/1078-0432.CCR-08-2439OAI: diva2:208924
Available from: 2009-03-21 Created: 2009-03-21 Last updated: 2009-03-21

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Brunk, Ulf
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Pharmacology Faculty of Health Sciences
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