Open Access

Propranolol induces hemangioma endothelial cell apoptosis via a p53‑BAX mediated pathway

  • Authors:
    • Tian‑Hua Yao
    • Parekejiang Pataer
    • Krishna Prasad Regmi
    • Xi‑Wen Gu
    • Quan‑Yan Li
    • Jing‑Ting Du
    • Su‑Meng Ge
    • Jun‑Bo Tu
  • View Affiliations

  • Published online on: May 14, 2018     https://doi.org/10.3892/mmr.2018.9013
  • Pages: 684-694
  • Copyright: © Yao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The use of propranolol for the treatment of infantile hemangioma (IH) has been widely investigated in recent years. However, the underlying therapeutic mechanism of propranolol for the treatment of IH remains poorly understood. The aim of the present study was to investigate the expression of proteins regulated by cellular tumor antigen p53 (p53) in associated apoptosis pathways in IH endothelial cells (HemECs) treated with propranolol. Furthermore, the present study aimed to investigate the exact apoptotic pathway underlying the therapeutic effect of propranolol against IH. In the present study, HemECs were subcultured and investigated using an inverted phase contrast microscope, immunocytochemical staining and a scanning electron microscope (SEM). Experimental groups and blank control groups were prepared. All groups were subjected to drug treatment. A high p53 expression model of HemECs was successfully established via transfection, and a low p53 expression model of HemECs was established using pifithrin‑α. The apoptosis rate of each group was determined using Annexin V‑fluorescein isothiocyanate/propidium iodide double staining and flow cytometry. The expression levels of downstream proteins regulated by p53 [tumour necrosis factor receptor superfamily member 6 (FAS), p53‑induced death domain‑containing protein (PIDD), death receptor 5 (DR5), BH3‑interacting domain death agonist (BID), apoptosis regulator BAX (BAX), p53 unregulated modulator of apoptosis (PUMA), phosphatidylinositol‑glycan biosynthesis class S protein (PIGS), and insulin‑like growth factor‑binding protein 3 (IGF‑BP3)] were revealed in the experimental and control groups via western blotting. Microscopic observation revealed the growth of an adherent monolayer of cells, which were closely packed and exhibited contact inhibition. Immunocytochemical staining demonstrated increased expression of clotting factor VIII. SEM analysis revealed presence of Weibel‑Palade bodies. The results of the analyses verified that the cultured cells were HemECs. The staining of the samples resulted in a significantly increased rate of apoptosis in experimental groups compared with the blank control group. This result suggested that there is an association between p53 expression and the rate of apoptosis of propranolol‑treated HemECs. The results of the western blot analysis demonstrated an upregulation of BAX expression and a downregulation of IGF‑BP3 expression in the HemECs treated with propranolol. There were no significant differences in the expression levels of FAS, DR5, PIDD, BID, PUMA and PIGS between experimental and control groups. This result suggests that p53 has an important role in HemEC apoptosis. The results of the present study additionally suggest that the propranolol‑induced HemEC apoptosis pathway is a mitochondrial apoptosis pathway and is regulated by p53‑BAX signaling.
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July-2018
Volume 18 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Yao TH, Pataer P, Regmi KP, Gu XW, Li QY, Du JT, Ge SM and Tu JB: Propranolol induces hemangioma endothelial cell apoptosis via a p53‑BAX mediated pathway . Mol Med Rep 18: 684-694, 2018
APA
Yao, T., Pataer, P., Regmi, K.P., Gu, X., Li, Q., Du, J. ... Tu, J. (2018). Propranolol induces hemangioma endothelial cell apoptosis via a p53‑BAX mediated pathway . Molecular Medicine Reports, 18, 684-694. https://doi.org/10.3892/mmr.2018.9013
MLA
Yao, T., Pataer, P., Regmi, K. P., Gu, X., Li, Q., Du, J., Ge, S., Tu, J."Propranolol induces hemangioma endothelial cell apoptosis via a p53‑BAX mediated pathway ". Molecular Medicine Reports 18.1 (2018): 684-694.
Chicago
Yao, T., Pataer, P., Regmi, K. P., Gu, X., Li, Q., Du, J., Ge, S., Tu, J."Propranolol induces hemangioma endothelial cell apoptosis via a p53‑BAX mediated pathway ". Molecular Medicine Reports 18, no. 1 (2018): 684-694. https://doi.org/10.3892/mmr.2018.9013