Huang Haizhi, Chen Allen Y, Rojanasakul Yon, Ye Xingqian, Rankin Gary O, Chen Yi Charlie
College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang University, China ; College of Science, Technology & Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA.
Department of Pharmaceutical Science, West Virginia University, Morgantown, WV 26506, USA.
J Funct Foods. 2015 May 1;15:464-475. doi: 10.1016/j.jff.2015.03.051.
Galangin and myricetin are flavonoids isolated from vegetables and fruits which exhibit anti-proliferative activity in human cancer cells. In this study, their anti-angiogenic effects were investigated with (HUVEC) and (CAM) models, which showed that galangin and myricetin inhibited angiogenesis induced by OVCAR-3 cells. The molecular mechanisms through which galangin and myricetin suppress angiogenesis were also studied. It was observed that galangin and myricetin inhibited secretion of the key angiogenesis mediator vascular endothelial growth factor (VEGF) and decreased levels of p-Akt, p-70S6K and hypoxia-inducible factor-1α (HIF-1α) proteins in A2780/CP70 and OVCAR-3 cells. Transient transfection experiments showed that galangin and myricetin inhibited secretion of VEGF by the Akt/p70S6K/ HIF-1α pathway. Moreover, a novel pathway, p21/HIF-1α/VEGF, was found to be involved in the inhibitory effect of myricetin on angiogenesis in OVCAR-3 cells. These data suggest that galangin and myricetin might serve as potential anti-angiogenic agents in the prevention of ovarian cancers dependent on new blood vessel networks.
高良姜素和杨梅素是从蔬菜和水果中分离出的黄酮类化合物,它们在人类癌细胞中具有抗增殖活性。在本研究中,利用人脐静脉内皮细胞(HUVEC)和鸡胚绒毛尿囊膜(CAM)模型研究了它们的抗血管生成作用,结果表明高良姜素和杨梅素可抑制由OVCAR-3细胞诱导的血管生成。还研究了高良姜素和杨梅素抑制血管生成的分子机制。观察到高良姜素和杨梅素可抑制关键血管生成介质血管内皮生长因子(VEGF)的分泌,并降低A2780/CP70和OVCAR-3细胞中p-Akt、p-70S6K和缺氧诱导因子-1α(HIF-1α)蛋白的水平。瞬时转染实验表明,高良姜素和杨梅素通过Akt/p70S6K/HIF-1α途径抑制VEGF的分泌。此外,还发现了一条新的途径p21/HIF-1α/VEGF参与杨梅素对OVCAR-3细胞血管生成的抑制作用。这些数据表明,高良姜素和杨梅素可能作为潜在的抗血管生成剂用于预防依赖新血管网络的卵巢癌。