Abstract | OBJECTIVE: Although oestrogen-related receptor alpha ( ERRalpha) is primarily thought to regulate energy homeostasis, it also serves as a prognostic marker for cancer. The aim of this study was to investigate any connection between ERRalpha activity and cell population growth. MATERIALS AND METHODS: RESULTS: We found that XCT-790 treatment reduced mitochondrial mass but enhanced mitochondrial ROS production by increasing rate through the TCA cycle, elevating mitochondrial membrane potential (DeltaPsi(m)) and down-regulating expression of superoxide dismutase. It was further demonstrated that XCT-790-induced ROS modulated p53 and Rb signalling pathways and suppressed cell replication. CONCLUSIONS:
ERRalpha affects cell cycle mechanisms through modulating mitochondrial mass and function. Dysregulation of this essential pathway leads to elevation in mitochondrial ROS production, which in turn modulates activities of tumour suppressors, resulting in cell cycle arrest.
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Authors | J Wang, Y Wang, C Wong |
Journal | Cell proliferation
(Cell Prolif)
Vol. 43
Issue 2
Pg. 103-13
(Apr 2010)
ISSN: 1365-2184 [Electronic] England |
PMID | 20447055
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzimidazoles
- Carbocyanines
- ERRalpha estrogen-related receptor
- Fluorescent Dyes
- Nitriles
- Reactive Oxygen Species
- Receptors, Estrogen
- Thiazoles
- Tumor Suppressor Protein p53
- XCT790
- 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine
- Superoxide Dismutase
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Topics |
- Benzimidazoles
(metabolism)
- Carbocyanines
(metabolism)
- Carcinoma, Non-Small-Cell Lung
(metabolism, pathology)
- Cell Cycle
- Cell Line, Tumor
- Dose-Response Relationship, Drug
- Fluorescent Dyes
(metabolism)
- Humans
- Lung
(metabolism, pathology)
- Lung Neoplasms
(metabolism, pathology)
- Membrane Potential, Mitochondrial
(drug effects)
- Membrane Potentials
(drug effects)
- Mitochondria
(drug effects)
- Nitriles
(pharmacology)
- Reactive Oxygen Species
(analysis, metabolism)
- Receptors, Estrogen
(agonists)
- Signal Transduction
(drug effects)
- Superoxide Dismutase
(metabolism)
- Thiazoles
(pharmacology)
- Time Factors
- Tumor Suppressor Protein p53
(metabolism)
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