Resveratrol inhibits obesity-associated adipose tissue dysfunction and tumor growth in a mouse model of postmenopausal claudin-low breast cancer.

Autor: Rossi EL; Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina., Khatib SA; Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina., Doerstling SS; Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina., Bowers LW; Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina., Pruski M; Department of Nutritional Sciences, University of Texas, Austin, Texas., Ford NA; Department of Nutritional Sciences, University of Texas, Austin, Texas., Glickman RD; Department of Ophthalmology, University of Texas Health Science Center, San Antonio, Texas., Niu M; College of Pharmacy, Pharmaceutics Division, University of Texas, Austin, Texas., Yang P; Department of Palliative, Rehabilitation and Integrative Medicine, M.D. Anderson Cancer Center, Houston, Texas., Cui Z; College of Pharmacy, Pharmaceutics Division, University of Texas, Austin, Texas., DiGiovanni J; Division of Pharmacology and Toxicology, The University of Texas, Austin, Texas., Hursting SD; Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
Jazyk: angličtina
Zdroj: Molecular carcinogenesis [Mol Carcinog] 2018 Mar; Vol. 57 (3), pp. 393-407. Date of Electronic Publication: 2017 Dec 01.
DOI: 10.1002/mc.22763
Abstrakt: Adipose tissue dysregulation, a hallmark of obesity, contributes to a chronic state of low-grade inflammation and is associated with increased risk and progression of several breast cancer subtypes, including claudin-low breast tumors. Unfortunately, mechanistic targets for breaking the links between obesity-associated adipose tissue dysfunction, inflammation, and claudin-low breast cancer growth have not been elucidated. Ovariectomized female C57BL/6 mice were randomized (n = 15/group) to receive a control diet, a diet-induced obesity (DIO) diet, or a DIO + resveratrol (0.5% wt/wt) diet. Mice consumed these diets ad libitum throughout study and after 6 weeks were orthotopically injected with M-Wnt murine mammary tumor cells, a model of estrogen receptor (ER)-negative claudin-low breast cancer. Compared with controls, DIO mice displayed adipose dysregulation and metabolic perturbations including increased mammary adipocyte size, cyclooxygenase-2 (COX-2) expression, inflammatory eicosanoid levels, macrophage infiltration, and prevalence of crown-like structures (CLS). DIO mice (relative to controls) also had increased systemic inflammatory cytokines and decreased adipocyte expression of peroxisome proliferator-activated receptor gamma (PPARγ) and other adipogenesis-regulating genes. Supplementing the DIO diet with resveratrol prevented obesity-associated increases in mammary tumor growth, mammary adipocyte hypertrophy, COX-2 expression, macrophage infiltration, CLS prevalence, and serum cytokines. Resveratrol also offset the obesity-associated downregulation of adipocyte PPARγ and other adipogenesis genes in DIO mice. Our findings suggest that resveratrol may inhibit obesity-associated inflammation and claudin-low breast cancer growth by inhibiting adipocyte hypertrophy and associated adipose tissue dysregulation that typically accompanies obesity.
(© 2017 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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