Association between obesity and breast cancer: Molecular bases and the effect of flavonoids in signaling pathways

Abstract

Obesity is an abnormal or excessive accumulation of fat that leads to different health problems, such as cancer, where the adipocytes promote the proliferation, migration, and invasion of cancer cells, especially in the breast, where the epithelial cells are immersed in a fatty environment, and the interactions between these two types of cells involve, not only adipokines but also local pro-inflammatory mechanisms and hypoxic processes generating anti-apoptotic signals, which are a common result in leptin signaling. The expression of the Vascular Endothelial Growth Factor (VEGF) and cyclin D1, results in the decrease in phosphorylation of AMPK, increasing the activity of the aromatase enzyme; alternatively, the adiponectin activates AMPK to reduce inflammation. Nevertheless, alterations of the JAK/STAT pathways contribute to mammary carcinogenesis, while the PI3K/AKT/mTOR pathway controls most of the cancer's characteristics such as the cell cycle, survival, differentiation, proliferation, motility, metabolism, and genetic stability. Therefore, the purpose of the present review is, through the accumulated scientific evidence, to find the concordance between the signaling pathways involved among obesity and breast cancer, which can be modulated by using flavonoids.

Keywords: Adipokines; Estrogens; Flavonoids; Obesity; Signaling Pathways.