Schempp Christoph M, Kiss Judit, Kirkin Vladimir, Averbeck Marco, Simon-Haarhaus Birgit, Kremer Bernhard, Termeer Christian C, Sleeman Jonathan, Simon Jan C
Department of Dermatology, University of Freiburg, Germany.
Planta Med. 2005 Nov;71(11):999-1004. doi: 10.1055/s-2005-871303.
Hyperforin is a plant compound from Hypericum perforatum that inhibits tumor cell proliferation in vitro by induction of apoptosis. Here, we report that hyperforin also acts as an angiogenesis inhibitor in vitro and in vivo. In vitro, hyperforin blocked microvessel formation of human dermal microvascular endothelial cells (HDMEC) on a complex extracellular matrix. Furthermore, hyperforin reduced proliferation of HDMEC in a dose-dependent manner, without displaying toxic effects or inducing apoptosis of the cells. To evaluate the antiangiogenic activity of hyperforin in vivo, Wistar rats were subcutaneously injected with MT-450 mammary carcinoma cells and were treated with peritumoral injections of hyperforin or solvent. Hyperforin significantly inhibited tumor growth, induced apoptosis of tumor cells and reduced tumor vascularization, as shown by in situ staining of CD31-positive microvessels in the tumor stroma. These data suggest that, in addition to the induction of tumor cell apoptosis, hyperforin can also suppress angiogenesis by a direct, non-toxic effect on endothelial cells.
金丝桃素是一种来自贯叶连翘的植物化合物，它通过诱导凋亡在体外抑制肿瘤细胞增殖。在此，我们报告金丝桃素在体外和体内还可作为血管生成抑制剂。在体外，金丝桃素可在复杂的细胞外基质上阻断人真皮微血管内皮细胞（HDMEC）的微血管形成。此外，金丝桃素以剂量依赖的方式降低HDMEC的增殖，且未表现出毒性作用或诱导细胞凋亡。为了评估金丝桃素在体内的抗血管生成活性，将Wistar大鼠皮下注射MT - 450乳腺癌细胞，并在肿瘤周围注射金丝桃素或溶剂进行治疗。如肿瘤基质中CD31阳性微血管的原位染色所示，金丝桃素显著抑制肿瘤生长，诱导肿瘤细胞凋亡并减少肿瘤血管生成。这些数据表明，除了诱导肿瘤细胞凋亡外，金丝桃素还可通过对内皮细胞的直接、无毒作用抑制血管生成。
