Β3-Adrenoreceptors Control Mitochondrial Dormancy in Melanoma and Embryonic Stem Cells. (13th November 2018)

• Record Type: Journal Article
• Authors: Calvani, Maura; Cavallini, Lorenzo; Tondo, Annalisa; Spinelli, Valentina; Ricci, Luisa; Pasha, Amada; Bruno, Gennaro; Buonvicino, Daniela; Bigagli, Elisabetta; Vignoli, Marina; Bianchini, Francesca; Sartiani, Laura; Lodovici, Maura; Semeraro, Roberto; Fontani, Filippo; De Logu, Francesco; Dal Monte, Massimo; Chiarugi, Paola; Favre, Claudio; Filippi, Luca
• Other Names: Peluso Ilaria Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2018(2018)
• Publication Date: 2018-11-13
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2018/6816508
• Languages: English
• ISSNs: 1942-0900

Abstract

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.