Acacetin inhibits expression of E-selectin on endothelial cells through regulation of the MAP kinase signaling pathway and activation of NF-κB

Abstract

Since E-selectin-mediated adhesion of leukocytes or tumor cells to the vascular endothelium is a key early event in the initiation of inflammatory response and cancer metastasis, E-selectin inhibition is thought to be a good target for therapeutic intervention. Several flavones have been shown to have anti-inflammatory and anticancer properties. In the present study, we investigated the effects of plant flavones on expression of E-selectin in human umbilical vein endothelial cells. Among 11 flavones, acacetin strongly inhibited TNF-α-induced E-selectin expression in HUVECs. Acacetin suppressed the TNF-α-induced phosphorylation of p38 but did not inhibit TNF-α-induced phosphorylations of JNK and ERK. Acacetin also inhibited the activation of NF-κB by stimulation with TNF-α. Furthermore, adhesion of monocytes to TNF-α-treated endothelial cells was inhibited by cotreatment with acacetin. These results suggest that acacetin inhibits the expression of E-selectin by regulation of the p38 MAPK signaling pathway and activation of NF-κB.

Acacetin Blocks Kv1.3 Channels and Inhibits Human T Cell Activation

“…However, whether Acacetin has a direct blocking effect on CRAC channels, through which Ca 2+ entry mediates T cell activation, requires further investigation. Acacetin may also directly target the inflammation-related transcription factors [34] or the inflammatory intermediates iNOS and COX-2 [2]. Consistent with these findings, in animal models, Acacetin can ameliorate autoimmune delayed-type hypersensitivity and have no obvious side effects [3].…”

Chitosan oligosaccharides downregulate the expression of E-selectin and ICAM-1 induced by LPS in endothelial cells by inhibiting MAP kinase signaling

“…Endothelial cells are the target of inflammatory responses and thereby, of a number of severe disorders, including sepsis and multiple organ dysfunctions that occur via LPS stimulation (11). In this study, we detected the expression of the adhesion molecules, E-selectin and ICAM-1 in LPS-treated porcine iliac artery endothelial cells (PIECs), since the upregulation of adhesion molecules and the increased secretion of cytokines and chemokines are known to occur during endothelial cell activation (12)(13)(14).…”

“…Endothelial cells are the target of inflammatory responses and thereby, of a number of severe disorders, including sepsis and multiple organ dysfunctions that occur via LPS stimulation (11). In this study, we detected the expression of the adhesion molecules, E-selectin and ICAM-1 in LPS-treated porcine iliac artery endothelial cells (PIECs), since the upregulation of adhesion molecules and the increased secretion of cytokines and chemokines are known to occur during endothelial cell activation (12)(13)(14).The evolutionary conserved family of mitogen-activated protein kinases (MAPKs) includes extracellular p38 MAPK, extracellular regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) (15). Numerous environmental stresses, such as osmotic shock, ultraviolet irradiation, as well as LPS and pro-inflammatory cytokines, have been confirmed to activate MAPK signaling cascades in a variety of cell lines (11,16).…”

The mechanism of acacetin-induced apoptosis on oral squamous cell carcinoma

“…Acacetin (5,7-dihydroxy-40-methoxyflavone) is present in many plants such as thistle, safflower seed, acacia, induces apoptosis and has been reported anti-peroxidative, anti-inflammatory, anti-plasmodial and anti-proliferative effect by blocking cell cycle progression. [28][29][30][31][32][33] Several recent studies showed that acacetin to inhibit the proliferation of A549 cells lung cancer cells and HepG2 human liver cancer by blocking the cell cycle progression. 31,34 Acacetin inhibited the growth of human breast cancer MCF-7 cells and inhibits cell growth and cell cycle progression, and induces apoptosis in human prostate cancer cells.…”