Martha A. Belury, Shana R. Straka, Rachel M. Cole, Lisa D. Yee, Jia-Yu Ke, Yung-Hsuan Hsiao, Taylor Banh
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.
Naringenin reduces adiposity and ameliorates adipose tissue inflammation, with a moderate inhibitory effect on tumor growth in obese ovariectomized mice.
Naringenin, a flavonoid found in citrus fruits, has exhibited anti-tumorigenic activity and ameliorated metabolic dysregulation. The present study shows that naringenin readily accumulates in mammary tumor and mammary adipose tissue. In addition, naringenin supplementation reduces body weight, adipose tissue mass, and adipose tissue inflammation, with resultant delays in mammary tumor growth in a mouse model of postmenopausal obesity.