Effects of novel safrole oxide derivatives, 1-propyl-3-(3,4-methylenedioxyphenyl)-2-propanol and 1-isopropoxy-3-(3,4-methylenedioxyphenyl)-2-propanol, on apoptosis induced by deprivation of survival factors in vascular endothelial cells.

Two safrole oxide derivatives, 1-propoxy-3-(3,4-methylenedioxyphenyl)-2-propanol (FOD) and 1-isopropoxy-3-(3,4-methylenedioxyphenyl)-2-propanol (GOD), were newly synthesized as promoters of apoptosis in vascular endothelial cells. The purpose of this study was to investigate the effects of these two safrole oxide derivatives on cell growth and apoptosis induced by deprivation of survival factors (serum and fibroblast growth factors, aFGF and bFGF) in vascular endothelial cells (VECs). MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium) method, agarose gel electrophoresis, laser scanning confocal microscopy, flow cytometry (FCM), and immunofluorescence assay were used. The cells deprived of FGF and serum were exposed to FOD or GOD 30 to 90 mg x L(-1) for 24 h, cell growth was suppressed (p < .05), whereas detachment and DNA fragmentation of these cells were promoted (p < .01). When the cells were treated with FOD 90 mg x L(-) for 24 h, apoptosis rate was 14.99% (p < .01). There were more cells in G2-M phase and less cells in S phase. At 90 mg x L(-1) concentration, GOD blocked 77.03%of the cells at G0-G1 phase., P53 level in VEC exposed to FOD or GOD was increased (p < .01). The data suggested that FOD and GOD might promote apoptosis of VEC by affect the cell cycle distribution, whereas P53 was involved in this pathway.