| Mitochondrial targeting overcomes ABCA1-dependent resistance of lung carcinoma to α-tocopheryl succinate. | |
| | |
MedLine Citation:
|
PMID: 23299931 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
α-Tocopheryl succinate (α-TOS) is a promising anti-cancer agent due to its selectivity for cancer cells. It is important to understand whether long-term exposure of tumour cells to the agent will render them resistant to the treatment. Exposure of the non-small cell lung carcinoma H1299 cells to escalating doses of α-TOS made them resistant to the agent due to the upregulation of the ABCA1 protein, which caused its efflux. Full susceptibility of the cells to α-TOS was restored by knocking down the ABCA1 protein. Similar resistance including ABCA1 gene upregulation was observed in the A549 lung cancer cells exposed to α-TOS. The resistance of the cells to α-TOS was overcome by its mitochondrially targeted analogue, MitoVES, that is taken up on the basis of the membrane potential, bypassing the enhanced expression of the ABCA1 protein. The in vitro results were replicated in mouse models of tumours derived from parental and resistant H1299 cells. We conclude that long-term exposure of cancer cells to α-TOS causes their resistance to the drug, which can be overcome by its mitochondrially targeted counterpart. This finding should be taken into consideration when planning clinical trials with vitamin E analogues. |
| | |
Authors:
|
Lubomir Prochazka; Stepan Koudelka; Lan-Feng Dong; Jan Stursa; Jacob Goodwin; Jiri Neca; Josef Slavik; Miroslav Ciganek; Josef Masek; Katarina Kluckova; Maria Nguyen; Jaroslav Turanek; Jiri Neuzil |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2013-1-9 |
Journal Detail:
|
Title: Apoptosis : an international journal on programmed cell death Volume: - ISSN: 1573-675X ISO Abbreviation: Apoptosis Publication Date: 2013 Jan |
Date Detail:
|
Created Date: 2013-1-9 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9712129 Medline TA: Apoptosis Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Veterinary Research Institute, Brno, Czech Republic, lubomir.pr@gmail.com. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Hypoxia-mediated sorafenib resistance can be overcome by EF24 through VHL-dependent HIF-1? inhibitio...
Next Document: Altered Cerebral Response During Cognitive Control: A Potential Indicator of Genetic Liability for S...