24-Methylenecycloartanyl Ferulate Protects against Expression of Pro-Angiogenesis Related Genes through Peroxisome Proliferator-Activated Receptor Gamma 2 in Human Breast Cancer MCF7 Cells - Abstract
Peroxisome proliferator-activated receptor gamma 2 (PPAR?2) has currently been considered as molecular target for angiogenesis signaling. Here, we investigated the effect
of 24-methylenecycloartanyl ferulate (24-MCF) induced PPAR?2 on expression of angiogenesis-related genes in MCF7 cells. cDNA microarray, real-time PCR revealed that 24-MCF
mediated the expression of genes related to angiogenesis in MCF-7 cells. We identified PPAR-response elements (PPRE) located in the LIF promoter regions (-1192 to -802), and
VEGF (-452 to +1). Luciferase reporter assay demonstrated that activation of the LIF gene, an anti-angiogenesis factor, was increased upon both 24-MCF treatment and PPAR?2
overexpression; whereas activation of VEGF promoters, known pro-angiogenesis factors, was decreased upon 24-MCF treatment and PPAR?2 overexpression. While these mutations
individually appeared to have no effect. Treatment with 24-MCF also decreased VEGF production in MCF7 cells and PMA-stimulated tube formation in HUVECs. Our findings suggest
that 24-MCF induces PPAR?2-mediated regulation of angiogenesis-related genes via PPRE motifs.