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Suppression of Tumo...
Suppression of Tumor Growth In vivo by the Mitocan alpha-tocopheryl Succinate Requires Respiratory Complex II
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- Dong, Lan-Feng (author)
- Griffith University
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- Freeman, Ruth (author)
- Griffith University
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- Liu, Ji (author)
- Griffith University
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- Zobalova, Renata (author)
- Griffith University
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- Marin-Hernandez, Alvaro (author)
- National Institute of Cardiology, Mexico City
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- Stantic, Marina (author)
- Griffith University
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- Rohlena, Jakub (author)
- Acadamy of Science, Czech Republic
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- Valis, Karel (author)
- Acadamy of Science, Czech Republic
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- Rodriguez-Enriquez, Sara (author)
- National Institute of Cardiology, Mexico City
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- Butcher, Bevan (author)
- Griffith University
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- Goodwin, Jacob (author)
- Griffith University
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- Brunk, Ulf (author)
- Linköpings universitet,Farmakologi,Hälsouniversitetet
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- Witting, Paul K (author)
- ANZAC Research Institute
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- Moreno-Sanchez, Rafael (author)
- National Institute of Cardiology, Mexico City
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- Scheffler, Immo E (author)
- University California at San Diego
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- Ralph, Stephen J (author)
- Griffith University
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- Neuzil, Jiri (author)
- Griffith University
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(creator_code:org_t)
- 2009
- 2009
- English.
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In: CLINICAL CANCER RESEARCH. - 1078-0432. ; 15:5, s. 1593-1600
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Keyword
- MEDICINE
- MEDICIN
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Dong, Lan-Feng
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Freeman, Ruth
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Liu, Ji
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Zobalova, Renata
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Marin-Hernandez, ...
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Stantic, Marina
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show more...
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Rohlena, Jakub
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Valis, Karel
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Rodriguez-Enriqu ...
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Butcher, Bevan
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Goodwin, Jacob
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Brunk, Ulf
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Witting, Paul K
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Moreno-Sanchez, ...
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Scheffler, Immo ...
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Ralph, Stephen J
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Neuzil, Jiri
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show less...
- Articles in the publication
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CLINICAL CANCER ...
- By the university
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Linköping University