Activated protein C inhibits bisphosphonate-induced endothelial cell death via the endothelial protein C receptor and nuclear factor-κB pathways

  • Authors:
    • Jae-Won Seol
    • You-Jin Lee
    • Christopher J. Jackson
    • Philip N. Sambrook
    • Sang-Youel Park
  • View Affiliations

  • Published online on: March 17, 2011     https://doi.org/10.3892/ijmm.2011.649
  • Pages: 835-840
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Abstract

Bisphosphonates promote apoptosis of cancer cells as well as osteoclasts in bone metastatic sites, but several clinical trials and high concentration treatment have shown that bisphosphonates have side effects that include bone loss and damage to normal cells. The aim of this study was to elucidate the protective effect and the possible mechanism of activated protein C (APC) against bisphosphonate-induced cell damage using primary cultured human umbilical vein endothelial cells (HUVECs). HUVECs were treated with APC (10 μg/ml) for 1 h, and then treated with bisphosphonates including alendronate, zoledronate and pamidronate. Bisphosphonates induced cell death in HUVECs but the cell death was blocked by treatment with APC. Bisphosphonates markedly induced caspase-3 activaion, which was diminished in cells exposed to APC. Matrix metalloproteinase-2 (MMP-2) reduction and nuclear factor-κB (NF-κB) activation induced by bisphosphonates in HUVECs were also blocked by APC treatment. Furthermore, APC highly induced the expression of the endothelial protein c receptor (EPCR) in HUVEC cells. In conclusion, the present study demonstrates that APC inhibits bisphosphonate-induced endothelial cell death via EPCR-induced inactivation of caspase-3 and NF-κB, and also suggests that APC has the potential to be a therapeutic drug in various vascular diseases induced by endothelial cell damage.

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June 2011
Volume 27 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Seol J, Lee Y, Jackson CJ, Sambrook PN and Park S: Activated protein C inhibits bisphosphonate-induced endothelial cell death via the endothelial protein C receptor and nuclear factor-κB pathways. Int J Mol Med 27: 835-840, 2011
APA
Seol, J., Lee, Y., Jackson, C.J., Sambrook, P.N., & Park, S. (2011). Activated protein C inhibits bisphosphonate-induced endothelial cell death via the endothelial protein C receptor and nuclear factor-κB pathways. International Journal of Molecular Medicine, 27, 835-840. https://doi.org/10.3892/ijmm.2011.649
MLA
Seol, J., Lee, Y., Jackson, C. J., Sambrook, P. N., Park, S."Activated protein C inhibits bisphosphonate-induced endothelial cell death via the endothelial protein C receptor and nuclear factor-κB pathways". International Journal of Molecular Medicine 27.6 (2011): 835-840.
Chicago
Seol, J., Lee, Y., Jackson, C. J., Sambrook, P. N., Park, S."Activated protein C inhibits bisphosphonate-induced endothelial cell death via the endothelial protein C receptor and nuclear factor-κB pathways". International Journal of Molecular Medicine 27, no. 6 (2011): 835-840. https://doi.org/10.3892/ijmm.2011.649