Suppressing Akt phosphorylation and activating Fas by safrole oxide inhibited angiogenesis and induced vascular endothelial cell apoptosis in the presence of fibroblast growth factor-2 and serum.
At present, vascular endothelial cell (VEC) apoptosis induced by deprivation of fibroblast growth factor-2 (FGF-2) and serum has been well studied. But how to trigger VEC apoptosis in the presence of FGF-2 and serum is not well known. To address this question, in this study, the effects of safrole oxide on angiogenesis and VEC growth stimulated by FGF-2 were investigated. The results showed that safrole oxide inhibited angiogenesis and induced VEC apoptosis in the presence of FGF-2 and serum. To understand the possible mechanism of safrole oxide acting, we first examined the phosphorylation of Akt and the activity of nitric oxide synthase (NOS); secondly, we analyzed the expressions and distributions of Fas and P53; then we measured the activity of phosphatidylcholine specific phospholipase C (PC-PLC) in the VECs treated with and without safrole oxide. The results showed that this small molecule obviously suppressed Akt phosphorylation and the activity of NOS, and promoted the expressions of Fas and P53 markedly. Simultaneously, Fas protein clumped on cell membrane, instead of homogenously distributed. The activity of PC-PLC was not changed obviously. The data suggested that safrole oxide effectively inhibited angiogenesis and triggered VEC apoptosis in the presence of FGF-2 and serum, and it might perform its functions by suppressing Akt/NOS signal pathway, upregulating the expressions of Fas and P53 and modifying the distributing pattern of Fas in VEC. This finding provided a powerful chemical probe for promoting VEC apoptosis during angiogenesis stimulated by FGF-2.
Zhao
Jing
J
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
Miao
Junying
J
Zhao
Baoxiang
B
Zhang
Shangli
S
Yin
Deling
D
D000818:Animals; D017209:Apoptosis; D053938:DNA Fragmentation; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D012451:Safrole / Q000031:analogs & derivatives* / Q000494:pharmacology; D044967:Serum / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D010738:Type C Phospholipases / Q000378:metabolism; D019014:fas Receptor / Q000502:physiology*
D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D016222:Fibroblast Growth Factor 2; C009196:safrole oxide; D019001:Nitric Oxide Synthase; D051057:Proto-Oncogene Proteins c-akt; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C; D012451:Safrole