Selective growth inhibition by sangivamycin of human umbilical vein endothelial cells

In the course of our screening for selective growth inhibitors of human umbilical vein endothelial cells (HUVECs), we isolated sangivamycin from the culture filtrate of Streptomyces. It inhibited the growth of HUVECs at approximately 30 times lower concentration than that needed to inhibit the growth of WI-38 human fibroblasts. Structurally-related nucleosides, such as toyocamycin, tubercidin, and formycins A and B, did not show the differential inhibition. Although sangivamycin is known to inhibit protein kinase C, other protein kinase C inhibitors did not inhibit the growth of HUVECs selectively. Sangivamycin effectively inhibited S-phase induction in HUVECs, like TNP-470 and LLnL, known selective inhibitors. However, unlike them sangivamycin did not induce p21 expression. On the other hand, sangivamycin was found to inhibit DNA synthesis selectively in HUVECs. Thus, sangivamycin was shown to be a new selective growth inhibitor of HUVECs acting on DNA synthesis.