6 research outputs found
Curcumin Modulates SDF-1/CXCR4–Induced Migration of Human Retinal Endothelial Cells (HRECs)
PURPOSE. The stromal-derived factor (SDF)-1 and the CXC
receptor (CXCR)-4 jointly regulate the trafficking of various cell
types and play a pivotal role in cell migration, proliferation, and
survival. The purpose of this study was to assess whether
curcumin inhibits human retinal endothelial cell (HREC) migration
by interfering with SDF-1/CXCR4 signaling.
METHODS. Primary HREC culture was established and maintained
in endothelial growth medium. The viability and proliferation
of HRECs were assessed by MTT and thymidine uptake
assays, respectively. The effect of SDF-1–induced HREC migration
(chemotaxis) in the presence and absence of curcumin
was determined using the Boyden chamber migration assay.
Intracellular Ca2 concentration was measured by fluorometric
analysis. Immunofluorescence and Western blot analyses
were performed to quantify CXCR4, phosphorylated AKT, and
PI3-kinase expression levels.
RESULTS. HREC migration increased in a dose-dependent manner
(1, 10, 50, and 100 ng/mL; P 0.001) in SDF-1–treated
cells. In contrast, AMD3100, an inhibitor of CXCR4 effectively
inhibited HREC migration dose dependently. HREC migration
was decreased when the cells were exposed to EGTA, a chelator
of Ca2. Curcumin also blocked Ca2 influx, an important
signal for HREC migration. In addition, curcumin significantly
(P 0.001) decreased SDF-1–induced HRECs migration and
downregulated SDF-1–induced expression of CXCR4, phospho-
AKT, phospho-phosphatidylinositol-3-kinase (PI3-K), and
eNOS.
CONCLUSIONS. This study indicates that curcumin has an inhibitory
effect on SDF-1–induced HREC migration. The plausible
mechanism of action could be upstream blockage of Ca2
influx and the downstream reduction of PI3-K/AKT signals