Protein kinase B inhibits endostatin-induced apoptosis in HUVECs.
Endostatin is a tumor-derived angiogenesis inhibitor, and the endogenous 20 kDa carboxyl-terminal fragment of collagen XVIII. In addition to inhibiting angiogenesis,endostatin inhibits tumor growth and the induction of apoptosis in several endothelial cell types. However, the mechanisms that regulate endostatin-induced apoptotic cell death are unclear. Here, we investigated apoptotic cell death and the underlying regulatory mechanisms elicited of endostatin in human umbilical vein endothelial cells (HUVECs). Endostatin was found to induce typical apoptotic features, such as, chromatin condensation and DNA fragmentation in these cells. Thus, as the phosphoinositide 3-OH kinase (PI3K)/protein kinase B (PKB) signaling pathway has been shown to prevent apoptosis in various cell types, we investigated whether this pathway could protect cells against endostatin induced apoptosis. It was found that the inhibition of PI3K/PKB significantly increased endostatin-induced apoptosis, and that endostatininduced cell death is physiologically linked to PKB-mediated cell survival through caspase-8.
Kang
Hee Young
HY
Division of Life Sciences, Chungbuk National University, Cheongju, 361-763, Korea.
Shim
Donghwan
D
Kang
Sang Sun
SS
Chang
Sook-Ik
SI
Kim
Hak Yong
HY
D000730:Androstadienes / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D043169:Endostatins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000077191:Wortmannin
D000730:Androstadienes; D043169:Endostatins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases; D000077191:Wortmannin