Liquorice alters adipocyte–breast cancer cell crosstalk by modulating oxidative stress and suppressing aromatase and renin–angiotensin signalling

Obesity is recognised to be a risk factor for breast cancer since adipose tissue influences the tumour microenvironment. This study aims to investigate the effect of the secretome of 3T3-L1 adipocytes untreated or treated with liquorice root extract (LRE), containing flavonoids, phenolic acids, and saponins on MCF-7 breast cancer cells. By treating adipocytes with LRE, the secretion of certain pro-tumorigenic factors like IGFBP-6, resistin, and VEGF was reduced. MCF-7 cells exposed to conditioned medium from LRE-treated adipocytes exhibited an increase in reactive oxygen species levels, downregulation of the Nrf2 antioxidant pathway, and increased autophagy. Those conditions reduced cell viability, migration, and colony formation. Additionally, there was downregulation of genes associated with oestrogen signalling and tumour-related processes, including CYP19A1 (aromatase), ERα, Her2, and components of the renin–angiotensin system (RAS). These findings suggest that LRE can modulate the adipocyte secretome to influence breast cancer cell behaviour under obesity-related in vitro conditions.