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β 3-Adrenoreceptors Control Mitochondrial Dormancy in Melanoma and Embryonic Stem Cells.
- Source :
-
Oxidative medicine and cellular longevity [Oxid Med Cell Longev] 2018 Nov 13; Vol. 2018, pp. 6816508. Date of Electronic Publication: 2018 Nov 13 (Print Publication: 2018). - Publication Year :
- 2018
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Abstract
- The early phases of embryonic development and cancer share similar strategies to improve their survival in an inhospitable environment: both proliferate in a hypoxic and catecholamine-rich context, increasing aerobic glycolysis. Recent studies show that β 3-adrenergic receptor ( β 3-AR) is involved in tumor progression, playing an important role in metastasis. Among β -adrenergic receptors, β 3-AR is the last identified member of this family, and it is involved in cancer cell survival and induction of stromal reactivity in the tumor microenvironment. β 3-AR is well known as a strong activator of uncoupling protein 1 (UCP1) in brown fat tissue. Interestingly, β 3-AR is strongly expressed in early embryo development and in many cancer tissues. Induction of uncoupling protein 2 (UCP2) has been related to cancer metabolic switch, leading to accelerated glycolysis and reduced mitochondrial activity. In this study, for the first time, we demonstrate that β 3-AR is able to promote this metabolic shift in both cancer and embryonic stem cells, inducing specific glycolytic cytoplasmic enzymes and a sort of mitochondrial dormancy through the induction of UCP2. The β 3-AR/UCP2 axis induces a strong reduction of mitochondrial activity by reducing ATP synthesis and mitochondrial reactive oxygen species (mtROS) content. These effects are reverted by SR59230A, the specific β 3-AR antagonist, causing an increase in mtROS. The increased level of mtROS is neutralized by a strong antioxidant activity in embryonic stem cells, but not in cancer stem cells, where it causes a dramatic reduction in tumor cell viability. These results lead to the possibility of a selective antitumor therapeutic use of SR59230A. Notably, we demonstrate the presence of β 3-AR within the mitochondrial membrane in both cell lines, leading to the control of mitochondrial dormancy.
- Subjects :
- Animals
Cell Line
Embryonic Stem Cells drug effects
Embryonic Stem Cells pathology
Humans
Melanoma pathology
Mice
Mitochondria drug effects
Receptors, Adrenergic, beta-3 metabolism
Adrenergic beta-3 Receptor Antagonists pharmacology
Embryonic Stem Cells metabolism
Melanoma metabolism
Mitochondria metabolism
Propanolamines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1942-0994
- Volume :
- 2018
- Database :
- MEDLINE
- Journal :
- Oxidative medicine and cellular longevity
- Publication Type :
- Academic Journal
- Accession number :
- 30538804
- Full Text :
- https://doi.org/10.1155/2018/6816508