Bai Xianhe, Cerimele Francesca, Ushio-Fukai Masuko, Waqas Muhammad, Campbell Paul M, Govindarajan Baskaran, Der Channing J, Battle Traci, Frank David A, Ye Keqiang, Murad Emma, Dubiel Wolfgang, Soff Gerald, Arbiser Jack L
Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Biol Chem. 2003 Sep 12;278(37):35501-7. doi: 10.1074/jbc.M302967200. Epub 2003 Jun 19.
Natural products comprise a major source of small molecular weight angiogenesis inhibitors. We have used the transformed endothelial cell line SVR as an effective screen of natural product extracts to isolate anti-angiogenesis and anti-tumor compounds. Aqueous extracts of Magnolia grandiflora exhibit potent activity in our SVR proliferation assays. We found that the small molecular weight compound honokiol is the active principle of magnolia extract. Honokiol exhibited potent anti-proliferative activity against SVR cells in vitro. In addition, honokiol demonstrated preferential inhibition of primary human endothelial cells compared with fibroblasts and this inhibition was antagonized by antibodies against TNF alpha-related apoptosis-inducing ligand. In vivo, honokiol was highly effective against angiosarcoma in nude mice. Our preclinical data suggests that honokiol is a systemically available and non-toxic inhibitor of angiogenesis and should be further evaluated as a potential chemotherapeutic agent.
天然产物是小分子血管生成抑制剂的主要来源。我们已将转化的内皮细胞系SVR用作天然产物提取物的有效筛选工具，以分离抗血管生成和抗肿瘤化合物。厚朴的水提取物在我们的SVR增殖试验中表现出强大的活性。我们发现小分子化合物厚朴酚是木兰提取物的活性成分。厚朴酚在体外对SVR细胞表现出强大的抗增殖活性。此外，与成纤维细胞相比，厚朴酚对原代人内皮细胞具有优先抑制作用，并且这种抑制作用可被抗TNFα相关凋亡诱导配体的抗体所拮抗。在体内，厚朴酚对裸鼠血管肉瘤非常有效。我们的临床前数据表明，厚朴酚是一种可全身应用且无毒的血管生成抑制剂，应作为潜在的化疗药物进行进一步评估。
