Jia-Yu Ke1,2, Taylor Banh1,2, Yung-Hsuan Hsiao1, Rachel M Cole1, Shana R Straka3, Lisa D Yee3, Martha A Belury1,2. 1. Department of Human Sciences, Human Nutrition program, College of Education and Human Ecology, The Ohio State University, Columbus, OH, USA. 2. The OSU Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, OH, USA. 3. Department of Surgery, College of Medicine, The Ohio State University, Columbus, OH, USA.
Abstract
SCOPE: Obesity-related metabolic dysregulation may be a link between obesity and postmenopausal breast cancer. Naringenin, a flavonoid abundant in grapefruits, displays beneficial effects on metabolic health and tumorigenesis. Here, we assessed the effects of naringenin on mammary tumor cell growth in vitro and in obese ovariectomized mice. METHODS AND RESULTS: Naringenin inhibited cell growth, increased phosphorylation of AMP-activated protein kinase (AMPK), down-regulated CyclinD1 expression, and induced cell death in E0771 mammary tumor cells. Obese ovariectomized mice were fed a high-fat (HF), high-fat diet with low naringenin (LN; 1% naringenin) or high-fat diet with high naringenin (HN; 3% naringenin) for 2 weeks and then implanted with E0771 cells in mammary adipose tissue. Three weeks after tumor cell implantation, naringenin accumulation in tumor was higher than that in mammary adipose tissue in HN mice. HN decreased body weight, adipose mass, adipocyte size, α-smooth muscle actin mRNA in mammary adipose tissue, and mRNA of inflammatory cytokines in both mammary and perigonadal adipose tissues. Compared with mice fed HF diet, HN delayed growth of tumors early but did not alter final tumor weight. CONCLUSION: Naringenin reduces adiposity and ameliorates adipose tissue inflammation, with a moderate inhibitory effect on tumor growth in obese ovariectomized mice.
SCOPE: Obesity-related metabolic dysregulation may be a link between obesity and postmenopausal breast cancer. Naringenin, a flavonoid abundant in grapefruits, displays beneficial effects on metabolic health and tumorigenesis. Here, we assessed the effects of naringenin on mammary tumor cell growth in vitro and in obese ovariectomized mice. METHODS AND RESULTS:Naringenin inhibited cell growth, increased phosphorylation of AMP-activated protein kinase (AMPK), down-regulated CyclinD1 expression, and induced cell death in E0771 mammary tumor cells. Obese ovariectomized mice were fed a high-fat (HF), high-fat diet with low naringenin (LN; 1% naringenin) or high-fat diet with high naringenin (HN; 3% naringenin) for 2 weeks and then implanted with E0771 cells in mammary adipose tissue. Three weeks after tumor cell implantation, naringenin accumulation in tumor was higher than that in mammary adipose tissue in HN mice. HN decreased body weight, adipose mass, adipocyte size, α-smooth muscle actin mRNA in mammary adipose tissue, and mRNA of inflammatory cytokines in both mammary and perigonadal adipose tissues. Compared with mice fed HF diet, HN delayed growth of tumors early but did not alter final tumor weight. CONCLUSION:Naringenin reduces adiposity and ameliorates adipose tissue inflammation, with a moderate inhibitory effect on tumor growth in obese ovariectomized mice.
Authors: Carla Holandino; Michelle Nonato de Oliveira Melo; Adriana Passos Oliveira; João Vitor da Costa Batista; Marcia Alves Marques Capella; Rafael Garrett; Mirio Grazi; Hartmut Ramm; Claudia Dalla Torre; Gerhard Schaller; Konrad Urech; Ulrike Weissenstein; Stephan Baumgartner Journal: BMC Complement Med Ther Date: 2020-07-09
Authors: Sinenhlanhla X H Mthembu; Phiwayinkosi V Dludla; Khanyisani Ziqubu; Tawanda M Nyambuya; Abidemi P Kappo; Evelyn Madoroba; Thembeka A Nyawo; Bongani B Nkambule; Sonia Silvestri; Christo J F Muller; Sithandiwe E Mazibuko-Mbeje Journal: Molecules Date: 2021-05-10 Impact factor: 4.411
Authors: Laura W Bowers; Claire G Lineberger; Nikki A Ford; Emily L Rossi; Arunima Punjala; Kristina K Camp; Bruce K Kimler; Carol J Fabian; Stephen D Hursting Journal: Breast Cancer Res Treat Date: 2018-10-26 Impact factor: 4.872