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

Two safrole oxide derivatives, 1-methoxy-3-(3,4-methylenedioxyphenyl)-2-propanol (MOD) and 1-ethoxy-3-(3,4-methylenedioxyphenyl)-2-propanol (EOD), were newly synthesized as promoters of apoptosis in vascular endothelial cells (VECs). 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 VECs. Morphological changes were observed with light microscopy. Cell growth was determined by using MTT (3-4, 5-dimethyl thiazol-2-yl]-2, 5-diphenytetrazolium) method. DNA fragmentation was analyzed by agarose gel electrophoresis and fluorescence microscopy. Apoptosis rate and cell cycle distribution were analyzed by flow cytometry (FCM). The cells deprived of FGF and serum were exposed to MOD 10-40 mg l(-1) for 24 h. Cell growth was suppressed (P<.01), while detachment and DNA fragmentation of these cells were promoted (P<.01). When the cells were treated with MOD30 mg l(-1) for 24 h, apoptosis rate was 21.43% (P<.01). The fact that 66.50% of the cells were trapped in S phase of cell cycle indicated that the cell cycle was blocked at S phase. Treated with EOD 10-40 mg l(-1) for 24 h, the cells were observed; the results showed that VEC growth was inhibited and the apoptosis was triggered (P<.01). At 30 mg l(-1) concentration, EOD blocked 55.22% of the cells at S phase. The data suggested that MOD and EOD might promote apoptosis of VEC by blocking the cell cycle at S phase.