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-jB 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.

Pluronic micelles encapsulated curcumin manifests apoptotic cell death and inhibits pro‐inflammatory cytokines in human breast adenocarcinoma cells

“…Further, we observed that PMsCur‐treated cells profoundly lose their MMP as compared with the free curcumin. It is well established that alteration in MMP leads to release of cytochrome c and activates downstream effector caspases for induction of apoptosis . Therefore, we examined the expression of cell death regulatory proteins including Bcl‐2, cytochrome c, caspase‐9, pro‐caspase‐7, and PARP.…”

High Mobility Group Box-1: A Missing Link between Diabetes and Its Complications

“…Besides, several other agents such as ethyl pyruvate [81], quercetin [88–90], atorvastatin [91], and simvastatin [92] were explored in various diseases by targeting HMGB-1; however, their protection effects in diabetes and its complications needed further investigations.…”

Hmgb1: A Potential Therapeutic Target for Non-Small Cell Lung Cancer

“…Anti-HMGB1 Antibody Extracellular HMGB1 Leukemia [8] Ethyl Pyruvate Extracellular HMGB1 Hepatocarcinoma [11] Glycyrrhizin Extracellular HMGB1 Melonoma [8] Oxaliplatin Intracellular HMGB1 Colon Carcinoma [12,13] Quercetin Extracellular HMGB1 Breast Cancer [9] HMGB1 in NSCLC As the previous studies showed, HMGB1 over expressed in NSCLC and affected the prognosis and development of NS-CLC patients. Because of the rare mutation of HMGB1 in NSCLC patients [3] , we considered HMGB1 as a better targeting bio-marker for NSCLC than TKs.…”

“…Besides of genetic suppress of HMGB1 expression in cancer cells, several targeting-HMGB1 agents have been used in experimental cancer research (see Table 1). Release of HMGB1 from cancer cells and necrotic cells during the progress of anti-cancer therapy has negative effects, so these agents include HMGB1 neutralizing antibody [8] quercetin [9] , glycyrrhizin [10] , ethylpyruvate [11] and oxaliplatin [12,13] may be conducive toward better outcomes in the treatment of cancer patients. Anti-HMGB1 antibody can inhibit the activity of extracellular HMGB1 in serum and tissues.…”

“…Anti-HMGB1 antibody can inhibit the activity of extracellular HMGB1 in serum and tissues. Small molecules like glycyrrhizin and quercetin which could directly bind to HMGB1which are used as potential HMGB1 inhibitors to enhance the effectiveness of anti-cancer drugs in several cancer models [9,14] . Meanwhile, oxaliplatin have the capacity to reduce the release of HMGB1 by retaining HMGB1 within the nucleus [12,13] .…”