Data from ACTIBIND, a T<sub>2</sub> RNase, Competes with Angiogenin and Inhibits Human Melanoma Growth, Angiogenesis, and Metastasis

<jats:p>&lt;div&gt;Abstract&lt;p&gt;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 &lt;i&gt;Aspergillus niger&lt;/i&gt;, termed ACTIBIND, that inhibits tumor growth and metastasis of melanoma &lt;i&gt;in vivo&lt;/i&gt;. ACTIBIND, a T&lt;sub&gt;2&lt;/sub&gt; 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 &lt;i&gt;in vivo&lt;/i&gt;. ACTIBIND significantly inhibited angiogenesis in an &lt;i&gt;in vivo&lt;/i&gt; angiogenesis assay with sponges containing angiogenin. &lt;i&gt;In vitro&lt;/i&gt;, 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. [Cancer Res 2007;67(11):5258–66]&lt;/p&gt;&lt;/div&gt;</jats:p>