Schwartz Betty, Shoseyov Oded, Melnikova Vladislava O, McCarty Marya, Leslie Michael, Roiz Levava, Smirnoff Patricia, Hu Guo-Fu, Lev Dina, Bar-Eli Menashe
The Institute of Biochemistry, Food Science, and Nutrition, Faculty of Agricultural, Food, and Environmental Quality Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Cancer Res. 2007 Jun 1;67(11):5258-66. doi: 10.1158/0008-5472.CAN-07-0129.
Melanoma is a very aggressive and highly angiogenic tumor in which standard treatments have had only limited success. Patients with advanced disease have a 5-year survival rate of 5%. In search for alternatives, we identified a natural product extracted from the fungus Aspergillus niger, termed ACTIBIND, that inhibits tumor growth and metastasis of melanoma in vivo. ACTIBIND, a T2 RNase, exerts antitumorigenic and antiangiogenic activities by competing with the angiogenic factor angiogenin (itself an RNase homologue). Thus, there was decreased expression and activity of the matrix metalloproteinase 2 in melanoma and vascular endothelial cells, decreased vascularization, and increased tumor cell apoptosis in vivo. ACTIBIND significantly inhibited angiogenesis in an in vivo angiogenesis assay with sponges containing angiogenin. In vitro, ACTIBIND was internalized by both melanoma and human umbilical vein endothelial cells, reached the cell nuclei, and inhibited the activity of angiogenin response elements in a dose-dependent manner. Collectively, our data indicate that ACTIBIND should be tested for its potential as a new antiangiogenic modality for the treatment of melanoma.
黑色素瘤是一种极具侵袭性且血管生成能力很强的肿瘤，标准治疗方法仅取得了有限的成功。晚期黑色素瘤患者的5年生存率为5%。为寻找替代方案，我们鉴定出一种从黑曲霉中提取的天然产物，名为ACTIBIND，它在体内可抑制黑色素瘤的肿瘤生长和转移。ACTIBIND是一种T2核糖核酸酶，通过与血管生成因子血管生成素（其本身是一种核糖核酸酶同源物）竞争发挥抗肿瘤和抗血管生成活性。因此，黑色素瘤和血管内皮细胞中基质金属蛋白酶2的表达和活性降低，血管生成减少，体内肿瘤细胞凋亡增加。在含血管生成素的海绵体内血管生成试验中，ACTIBIND显著抑制血管生成。在体外，ACTIBIND被黑色素瘤细胞和人脐静脉内皮细胞摄取，进入细胞核，并以剂量依赖方式抑制血管生成素反应元件的活性。总体而言，我们的数据表明，应测试ACTIBIND作为治疗黑色素瘤的新型抗血管生成药物的潜力。
