Quercetin protects necrotic insult and promotes apoptosis by attenuating the expression of RAGE and its ligand HMGB1 in human breast adenocarcinoma cells

The receptor for advanced glycation end‐products (RAGE) is a multiligand member of the immunoglobulin superfamily, which plays an important role in maintaining cellular homeostasis. It is normally expressed on immune cells, including macrophages, monocytes, dendritic cells and T cells to maintain homeostasis, but highly upregulated at sites of vascular pathology. Accumulating evidence suggest that the elevated expression of RAGE and its ligand HMGB‐1 was found in various types of cancer. The accumulation of RAGE and its ligand high‐mobility group box proteins‐1 (HMGB1) activates complex signaling network for cell survival and evades apoptosis. Therefore, targeting the RAGE‐mediated signaling could be the promising strategies for the therapeutic potential of cancer. This study was aimed to examine the biological potential of quercetin on the regulation of RAGE‐ and HMGB1‐mediated activation of NF‐κB and induction of apoptotic cell death in MCF‐7 cells. Our findings demonstrate that quercetin inhibits the expression of RAGE and HMGB1 in MCF‐7 cells. In addition, quercetin protects necrotic insult and augments apoptosis in MCF‐7 cells. Taken together, these results suggest that quercetin plays an important role in modulating RAGE and HMGB1 signaling and induces apoptotic cell death in MCF‐7 cells. © 2015 IUBMB Life, 2015 67(5):361–373, 2015