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Protein kinase B inhibits endostatin-induced apoptosis in HUVECs

Hee Young Kang1, Donghwan Shim, Sang Sun Kang

  • 1Division of Life Sciences, Chungbuk National University, Cheongju, 361-763, Korea.

Journal of Biochemistry and Molecular Biology
|February 10, 2006
PubMed

Insights

Endostatin, an angiogenesis inhibitor, induces apoptosis in endothelial cells. Blocking the PI3K/PKB pathway enhances this cell death, revealing a link to caspase-8 mediated survival.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Endostatin is a tumor-derived angiogenesis inhibitor and a fragment of collagen XVIII.
  • Endostatin inhibits tumor growth and induces apoptosis in endothelial cells.
  • The precise mechanisms of endostatin-induced apoptosis are not fully understood.

Purpose of the Study:

  • To investigate the mechanisms of endostatin-induced apoptotic cell death in human umbilical vein endothelial cells (HUVECs).
  • To determine the role of the phosphoinositide 3-OH kinase (PI3K)/protein kinase B (PKB) signaling pathway in endostatin-induced apoptosis.

Main Methods:

  • Induction of apoptosis in HUVECs using endostatin.
  • Inhibition of the PI3K/PKB signaling pathway.
  • Assessment of apoptotic features like chromatin condensation and DNA fragmentation.
  • Analysis of the involvement of caspase-8.

Main Results:

  • Endostatin induced typical apoptotic features in HUVECs.
  • Inhibition of the PI3K/PKB pathway significantly enhanced endostatin-induced apoptosis.
  • Endostatin-induced cell death was linked to PKB-mediated cell survival via caspase-8.

Conclusions:

  • The PI3K/PKB signaling pathway plays a crucial role in protecting endothelial cells against endostatin-induced apoptosis.
  • Endostatin-induced apoptosis is regulated by the interplay between PKB-mediated survival and caspase-8 activation.

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