dc.contributor.author | Dong, Lan-Feng | |
dc.contributor.author | Freeman, Ruth | |
dc.contributor.author | Liu, Ji | |
dc.contributor.author | Zobalova, Renata | |
dc.contributor.author | Marin-Hernandez, Alvaro | |
dc.contributor.author | Stantic, Marina | |
dc.contributor.author | Rohlena, Jakub | |
dc.contributor.author | Valis, Karel | |
dc.contributor.author | Rodriguez-Enriquez, Sara | |
dc.contributor.author | Butcher, Bevan | |
dc.contributor.author | Goodwin, Jacob | |
dc.contributor.author | Brunk, Ulf T | |
dc.contributor.author | Witting, Paul K | |
dc.contributor.author | Moreno-Sanchez, Rafael | |
dc.contributor.author | Scheffler, Immo E | |
dc.contributor.author | Ralph, Stephen J | |
dc.contributor.author | Neuzil, Jiri | |
dc.date.accessioned | 2017-05-03T15:05:20Z | |
dc.date.available | 2017-05-03T15:05:20Z | |
dc.date.issued | 2009 | |
dc.date.modified | 2010-06-07T08:05:53Z | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-08-2439 | |
dc.identifier.uri | http://hdl.handle.net/10072/30091 | |
dc.description.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 a-tocopoheryl succinate (a-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 a-TOS was studied. Results: The CII-functional and CII-reconstituted cells, unlike their CII-dysfunctional counterparts, responded to a-TOS by reactive oxygen species generation and apoptosis execution. Tumors derived from these cell lines reciprocated their responses to a-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, a-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. | |
dc.description.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.format.extent | 111326 bytes | |
dc.format.mimetype | application/pdf | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | American Association for Cancer Research | |
dc.publisher.place | USA | |
dc.relation.ispartofstudentpublication | N | |
dc.relation.ispartofpagefrom | 1593 | |
dc.relation.ispartofpageto | 1600 | |
dc.relation.ispartofissue | 5 | |
dc.relation.ispartofjournal | Clinical Cancer Research | |
dc.relation.ispartofvolume | 15 | |
dc.rights.retention | Y | |
dc.subject.fieldofresearch | Oncology and carcinogenesis | |
dc.subject.fieldofresearch | Molecular targets | |
dc.subject.fieldofresearch | Clinical sciences | |
dc.subject.fieldofresearchcode | 3211 | |
dc.subject.fieldofresearchcode | 321108 | |
dc.subject.fieldofresearchcode | 3202 | |
dc.title | Suppression of Tumor Growth In vivo by the Mitocan α-tocopheryl Succinate Requires Respiratory Complex II | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.faculty | Griffith Health, School of Medical Science | |
gro.rights.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. | |
gro.date.issued | 2009 | |
gro.hasfulltext | Full Text | |
gro.griffith.author | Neuzil, Jiri | |
gro.griffith.author | Ralph, Stephen J. | |