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Article Open Access

Zoledronate induces autophagic cell death in human umbilical vein endothelial cells via Beclin-1 dependent pathway activation

  • Authors:
    • Yong Lu
    • Zhiyong Wang
    • Wei Han
    • Hao Li
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China
    Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4747-4754
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    Published online on: October 12, 2016
       https://doi.org/10.3892/mmr.2016.5834
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Abstract

Zoledronate has been reported to exhibit pro‑apoptotic and anti-angiogenic effects in endothelial cells, which partially contributes to bisphosphonate‑associated osteonecrosis of the jaw (BP‑ONJ). Zoledronate can also induce autophagic cell death. The present study hypothesized that Zoledronate may activate autophagy to exert pro‑apoptotic effects in endothelial cells and aimed to investigate the effect of Zoledronate on human umbilical vein endothelial cells (HUVECs) and explore the underlying mechanisms. The current study demonstrated that Zoledronate induced autophagy in HUVECs in a dose‑dependent manner, as demonstrated by increased levels of microtubule‑associated proteins 1A/1B light chain 3B‑II (LC3B‑II) and Beclin‑1, and decreased levels of sequestome 1 (SQSTM1). In addition, treatment with chloroquine further increased LC3B‑II and increased SQSTM1 levels, indicating that Zoledronate induces autophagy by increasing autophagic activity. Flow cytometry and Hoechst 33258 staining revealed that inhibition of autophagy with 3-methyladenine markedly attenuated Zoledronate‑induced apoptosis. Furthermore, genetic knockdown of Beclin‑1 significantly inhibited autophagy and apoptosis induced by Zoledronate. The present study therefore demonstrated that Zoledronate may promote Beclin‑1‑mediated autophagy to induce endothelial cell apoptosis, and suggests that blocking autophagy may represent a novel approach for the prevention of BP‑ONJ in patients receiving Zoledronate.
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Copy and paste a formatted citation
Spandidos Publications style
Lu Y, Wang Z, Han W and Li H: Zoledronate induces autophagic cell death in human umbilical vein endothelial cells via Beclin-1 dependent pathway activation. Mol Med Rep 14: 4747-4754, 2016.
APA
Lu, Y., Wang, Z., Han, W., & Li, H. (2016). Zoledronate induces autophagic cell death in human umbilical vein endothelial cells via Beclin-1 dependent pathway activation. Molecular Medicine Reports, 14, 4747-4754. https://doi.org/10.3892/mmr.2016.5834
MLA
Lu, Y., Wang, Z., Han, W., Li, H."Zoledronate induces autophagic cell death in human umbilical vein endothelial cells via Beclin-1 dependent pathway activation". Molecular Medicine Reports 14.5 (2016): 4747-4754.
Chicago
Lu, Y., Wang, Z., Han, W., Li, H."Zoledronate induces autophagic cell death in human umbilical vein endothelial cells via Beclin-1 dependent pathway activation". Molecular Medicine Reports 14, no. 5 (2016): 4747-4754. https://doi.org/10.3892/mmr.2016.5834
Copy and paste a formatted citation
x
Spandidos Publications style
Lu Y, Wang Z, Han W and Li H: Zoledronate induces autophagic cell death in human umbilical vein endothelial cells via Beclin-1 dependent pathway activation. Mol Med Rep 14: 4747-4754, 2016.
APA
Lu, Y., Wang, Z., Han, W., & Li, H. (2016). Zoledronate induces autophagic cell death in human umbilical vein endothelial cells via Beclin-1 dependent pathway activation. Molecular Medicine Reports, 14, 4747-4754. https://doi.org/10.3892/mmr.2016.5834
MLA
Lu, Y., Wang, Z., Han, W., Li, H."Zoledronate induces autophagic cell death in human umbilical vein endothelial cells via Beclin-1 dependent pathway activation". Molecular Medicine Reports 14.5 (2016): 4747-4754.
Chicago
Lu, Y., Wang, Z., Han, W., Li, H."Zoledronate induces autophagic cell death in human umbilical vein endothelial cells via Beclin-1 dependent pathway activation". Molecular Medicine Reports 14, no. 5 (2016): 4747-4754. https://doi.org/10.3892/mmr.2016.5834
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