Suppression of Tumor Growth In vivo by the Mitocan α-tocopheryl Succinate Requires Respiratory Complex II

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Title Suppression of Tumor Growth In vivo by the Mitocan α-tocopheryl Succinate Requires Respiratory Complex II
Author Dong, Lan-feng; Freeman, Ruth; Liu, Ji; Zobalova, Renata; Marin-Hernandez, Alvaro; Stantic, Marina; Rohlena, Jakub; Valis, Karel; Rodriguez-Enriquez, Sara; Butcher, Bevan; Goodwin, Jacob; Brunk, Ulf T.; Witting, Paul K.; Moreno-Sanchez, Rafael; Scheffler, Immo E.; Ralph, Stephen John; Neuzil, Jiri
Journal Name Clinical Cancer Research
Year Published 2009
Place of publication USA
Publisher American Association for Cancer Research
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 α-tocopoheryl succinate (α-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 α-TOS was studied. Results: The CII-functional and CII-reconstituted cells, unlike their CII-dysfunctional counterparts, responded to α-TOS by reactive oxygen species generation and apoptosis execution. Tumors derived from these cell lines reciprocated their responses to α-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, α-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.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1158/1078-0432.CCR-08-2439
Copyright Statement Copyright 2009 AACR. This is the author-manuscript version of the paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal link for access to the definitive, published version.
Volume 15
Issue Number 5
Page from 1593
Page to 1600
ISSN 1078-0432
Date Accessioned 2010-02-11
Date Available 2010-06-07T08:05:53Z
Language en_AU
Research Centre Griffith Health Institute; Molecular Basis of Disease
Faculty Griffith Health Faculty
Subject Molecular Targets
URI http://hdl.handle.net/10072/30091
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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