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Suppression of Tumo...
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Dong, Lan-FengGriffith University
(author)
Suppression of Tumor Growth In vivo by the Mitocan alpha-tocopheryl Succinate Requires Respiratory Complex II
- Article/chapterEnglish2009
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Numbers
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LIBRIS-ID:oai:DiVA.org:liu-17382
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-17382URI
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https://doi.org/10.1158/1078-0432.CCR-08-2439DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
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Freeman, RuthGriffith University
(author)
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Liu, JiGriffith University
(author)
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Zobalova, RenataGriffith University
(author)
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Marin-Hernandez, AlvaroNational Institute of Cardiology, Mexico City
(author)
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Stantic, MarinaGriffith University
(author)
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Rohlena, JakubAcadamy of Science, Czech Republic
(author)
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Valis, KarelAcadamy of Science, Czech Republic
(author)
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Rodriguez-Enriquez, SaraNational Institute of Cardiology, Mexico City
(author)
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Butcher, BevanGriffith University
(author)
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Goodwin, JacobGriffith University
(author)
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Brunk, UlfLinköpings universitet,Farmakologi,Hälsouniversitetet(Swepub:liu)ulfbr20
(author)
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Witting, Paul KANZAC Research Institute
(author)
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Moreno-Sanchez, RafaelNational Institute of Cardiology, Mexico City
(author)
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Scheffler, Immo EUniversity California at San Diego
(author)
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Ralph, Stephen JGriffith University
(author)
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Neuzil, JiriGriffith University
(author)
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Griffith UniversityNational Institute of Cardiology, Mexico City
(creator_code:org_t)
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In:CLINICAL CANCER RESEARCH15:5, s. 1593-16001078-0432
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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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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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Linköping University