title: Quercetin protects necrotic insult and promotes apoptosis by attenuating the expression of RAGE and its ligand HMGB1 in human breast adenocarcinoma cells.
abstract: 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.
authors.affiliation: Department of Cell Biology, School of Biological Sciences & Biotechnology, Indian Institute of Advanced Research, Koba, Gandhinagar, India.
authors.forename: Suhashini S
authors.initials: SS
authors.lastname: Dhumale
authors.affiliation: Department of Cell Biology, School of Biological Sciences & Biotechnology, Indian Institute of Advanced Research, Koba, Gandhinagar, India.
authors.forename: Bhargav N
authors.initials: BN
authors.lastname: Waghela
authors.affiliation: Department of Cell Biology, School of Biological Sciences & Biotechnology, Indian Institute of Advanced Research, Koba, Gandhinagar, India.
authors.forename: Chandramani
authors.initials: C
authors.lastname: Pathak
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009336:Necrosis; D011794:Quercetin / Q000494:pharmacology*; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011794:Quercetin
keywords: HMGB1; RAGE; apoptosis; cancer; necrosis; quercetin