Toi Masakazu, Bando Hiroko, Ramachandran Cheppail, Melnick Steven J, Imai Atsushi, Fife Rose S, Carr Raymond Eric, Oikawa Tsutomu, Lansky Ephraim Philip
Department of Surgery, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan.
Angiogenesis. 2003;6(2):121-8. doi: 10.1023/B:AGEN.0000011802.81320.e4.
We previously showed pomegranate seed oil and fermented juice polyphenols to retard oxidation and prostaglandin synthesis, to inhibit breast cancer cell proliferation and invasion, and to promote breast cancer cell apoptosis. Here we evaluated the anti-angiogenic potential of these materials in several ways. We checked a possible effect on angiogenic regulation by measuring vascular endothelial growth factor (VEGF), interleukin-4 (IL-4) and migration inhibitory factor (MIF) in the conditioned media of estrogen sensitive (MCF-7) or estrogen resistant (MDA-MB-231) human breast cancer cells, or immortalized normal human breast epithelial cells (MCF-10A), grown in the presence or absence of pomegranate seed oil (SESCO) or fermented juice polyphenols (W). VEGF was strongly downregulated in MCF-10A and MCF-7, and MIF upregulated in MDA-MB-231, overall showing significant potential for downregulation of angiogenesis by pomegranate fractions. An anti-proliferative effect on angiogenic cells was shown in human umbilical vein endothelial cell (HUVEC) and in myometrial and amniotic fluid fibroblasts, and inhibition of HUVEC tubule formation demonstrated in an in vitro model employing glass carrier beads. Finally, we showed a significant decrease in new blood vessel formation using the chicken chorioallantoic membrane (CAM) model in vivo. 'In sum, these varied studies employing different models in different laboratories overall demonstrate for the first time an anti-angiogenic potential of pomegranate fractions, suggesting further in vivo and clinical investigations (for updates: info@rimonest.com).
我们之前的研究表明，石榴籽油和发酵汁多酚可延缓氧化和前列腺素合成，抑制乳腺癌细胞增殖和侵袭，并促进乳腺癌细胞凋亡。在此，我们通过多种方式评估了这些物质的抗血管生成潜力。我们通过测量雌激素敏感（MCF-7）或雌激素抵抗（MDA-MB-231）人乳腺癌细胞，或永生化正常人乳腺上皮细胞（MCF-10A）在有或无石榴籽油（SESCO）或发酵汁多酚（W）存在的条件培养基中的血管内皮生长因子（VEGF）、白细胞介素-4（IL-4）和迁移抑制因子（MIF），来检查其对血管生成调节的可能影响。在MCF-10A和MCF-7中VEGF被强烈下调，在MDA-MB-231中MIF被上调，总体显示石榴提取物具有显著的下调血管生成的潜力。在人脐静脉内皮细胞（HUVEC）以及子宫肌层和成羊水成纤维细胞中显示出对血管生成细胞的抗增殖作用，并在使用玻璃载体珠的体外模型中证明了对HUVEC小管形成的抑制作用。最后，我们在体内使用鸡胚绒毛尿囊膜（CAM）模型显示新血管形成显著减少。总之，这些在不同实验室采用不同模型的多样化研究首次总体证明了石榴提取物的抗血管生成潜力，提示进一步的体内和临床研究（最新信息：info@rimonest.com）。
