Dell'Eva Raffaella, Pfeffer Ulrich, Vené Roberta, Anfosso Luca, Forlani Alessandra, Albini Adriana, Efferth Thomas
Molecular Oncology, National Cancer Research Institute (IST), Largo Rosanna Benzi 10, 16132 Genova, Italy.
Biochem Pharmacol. 2004 Dec 15;68(12):2359-66. doi: 10.1016/j.bcp.2004.08.021.
Artesunate (ART) is a semi-synthetic derivative of the sesquiterpene artemisinin used for the second line therapy of malaria infections with Plasmodium falciparum. ART also inhibits growth of many transformed cell lines. In the present investigation, we show that ART inhibited the growth of normal human umbilical endothelial cells and of KS-IMM cells that we have established from a Kaposi's sarcoma lesion obtained from a renal transplant patient. The growth inhibitory activity correlated with the induction of apoptosis in KS-IMM cells. Apoptosis was not observed in normal endothelial cells, which, however, showed drastically increased cell doubling times upon ART treatment. ART strongly reduced angiogenesis in vivo in terms of vascularization of Matrigel plugs injected subcutaneously into syngenic mice. We conclude that ART represents a promising candidate drug for the treatment of the highly angiogenic Kaposi's sarcoma. As a low-cost drug, it might be of particular interest for areas of Kaposi's sarcoma endemics. ART could be useful for the prevention of tumor angiogenesis.
青蒿琥酯（ART）是倍半萜青蒿素的半合成衍生物，用于恶性疟原虫疟疾感染的二线治疗。ART还能抑制多种转化细胞系的生长。在本研究中，我们发现ART抑制正常人脐内皮细胞以及我们从一名肾移植患者的卡波西肉瘤病变中建立的KS-IMM细胞的生长。生长抑制活性与KS-IMM细胞中凋亡的诱导相关。在正常内皮细胞中未观察到凋亡，然而，经ART处理后，正常内皮细胞的细胞倍增时间大幅增加。就皮下注射到同基因小鼠体内的基质胶栓的血管形成而言，ART在体内强烈减少血管生成。我们得出结论，ART是治疗高血管生成性卡波西肉瘤的一种有前景的候选药物。作为一种低成本药物，它可能对卡波西肉瘤流行地区特别有意义。ART可能有助于预防肿瘤血管生成。
