Hesperidin, hesperidin methyl chalone and phellopterin from Poncirus trifoliata (Rutaceae) differentially regulate the expression of adhesion molecules in tumor necrosis factor-α-stimulated human umbilical vein endothelial cells

Flavonoids from Citrus unshiu Marc. inhibit cancer cell adhesion to endothelial cells by selective inhibition of VCAM-1

“…Of note, however, FCM suppressed the TNF-α-induced expression of VCAM-1, but not of ICAM-1. Relating to this result, there is a previous study demonstrating that hesperidin selectively inhibited TNF-induced VCAM-1 expression through suppressing PKC pathway, leading to inhibition of the adhesion of U937 leukemic cells to HUVECs (16). This result is consistent with our results showing the preferential inhibition of VCAM-1 expression over ICAM-1 by FCM.…”

Genipin Selectively Inhibits TNF-α-activated VCAM-1 But Not ICAM-1 Expression by Upregulation of PPAR-γ in Human Endothelial Cells

“…Or inhibition of phosphorylation of Akt and PKC could be involved in selective inhibition of VCAM-1 expression. These speculations come from our previous reports that PI3K/Akt and PKC signaling pathways are involved in VCAM-1 induction but not ICAM-1 in HUVEC [7,8]. Therefore, inhibition of phosphorylation of these signal molecules (Akt, PKC) can be another possible mechanism for this differential expression.…”

“…The medium was refreshed before stimulation with TNF-α. U937 monocytes ( 3×10 7 ) were incubated in RPMI 1640 medium containing 2% FBS and 10 mg/ml of the fluorescent dye BCECF/AM (Boehringer, Mannheim, Germany) at 37 o C for 30 min, as described previously [7]. Fluorescence-labeled cells were pelleted and resuspended (7.5×10 5 /ml) DMEM.…”

“…In addition to PPAR-activators, signal molecules and kinases such as PI3K/Akt, PKC, and ERK1/2 inhibitors also showed differential effects on ICAM-1 and VCAM-1 expression [7,8]. Therefore, we explored the effect of genipin on the TNF-α-induced phosphorylation of these signal molecules.…”

“…We [5] and others [6] suggested that activators of peroxisome proliferator-activated receptor (PPAR) can selectively inhibit the induction of vascular cell adhesion molecule-1 (VCAM-1), but not intercellular cell adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVEC). Moreover, we [7,8] suggested that PI3K/ PTEN, mitogen-activated protein kinases (MAPK) signals also differentially regulate the expression of adhesion molecules in lipopolysaccharide-or TNF-α-treated EC. Therefore, it is at least theoretically possible that any chemical which modifies activities of PPAR or PI3K or MAP kinases in EC can selectively inhibits VCAM-1 expression.…”