Effect and mechanisms of celastrol on the apoptosis of HOS osteosarcoma cells

  • Authors:
    • Yanyang Chen
    • Yunsheng Ou
    • Yong Tao
    • Huzhe Liu
    • Hang Yin
    • Shenxi Zhong
    • Haoyang Yu
    • Zenghui Zhao
    • Bin He
  • View Affiliations

  • Published online on: August 1, 2018     https://doi.org/10.3892/or.2018.6619
  • Pages: 2260-2268
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Abstract

Osteosarcoma is the most common primary malignant tumor of the bone found predominantly in children and teenagers and results in early metastasis and poor prognosis. The present study primarily focused on the impact of celastrol on apoptosis and autophagy of osteosarcoma HOS cells, as well as the related mechanisms. Following the appropriate treatment, the human osteosarcoma cell line HOS was assessed for viability, Ca2+ in cells, apoptosis and changes in cell morphology using Cell Counting Kit-8, flow cytometry, inverted phase contrast microscope, Hoechst staining and transmission electron microscopy. The expression levels of various proteins, including endoplasmic reticulum stress (ERS)-related proteins (Bip, PERK, p-PERK, IRE1α, calnexin, PDI and Erol‑Lα), apoptosis-related proteins (CHOP, cleaved caspase‑12), mitochondrial apoptosis-related proteins (Bax, Bcl-2 and cytochrome c), cleaved caspase-3, and autophagy-related proteins (LC3-Ⅰ, LC3-Ⅱ and P62) and β-actin, were assessed with western blotting. Celastrol significantly inhibited the viability of HOS cells in a dose-dependent manner and promoted the expression of ERS-related, apoptosis-related and mitochondrial apoptosis-related proteins. The ERS inhibitor tauroursodeoxycholate promoted celastrol-induced autophagy and apoptosis of HOS cells. Pretreatment with the PERK inhibitor GSK2656157 significantly promoted celastrol-induced death and attenuated HOS cell autophagy. Our results indicated that the ERS pathway and the mitochondrial pathway were involved in celastrol-induced apoptosis of HOS cells. The ERS/PERK pathway may protect HOS cells from apoptosis by celastrol and may play a complicated role in the process of autophagy.
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October-2018
Volume 40 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Chen Y, Ou Y, Tao Y, Liu H, Yin H, Zhong S, Yu H, Zhao Z and He B: Effect and mechanisms of celastrol on the apoptosis of HOS osteosarcoma cells. Oncol Rep 40: 2260-2268, 2018
APA
Chen, Y., Ou, Y., Tao, Y., Liu, H., Yin, H., Zhong, S. ... He, B. (2018). Effect and mechanisms of celastrol on the apoptosis of HOS osteosarcoma cells. Oncology Reports, 40, 2260-2268. https://doi.org/10.3892/or.2018.6619
MLA
Chen, Y., Ou, Y., Tao, Y., Liu, H., Yin, H., Zhong, S., Yu, H., Zhao, Z., He, B."Effect and mechanisms of celastrol on the apoptosis of HOS osteosarcoma cells". Oncology Reports 40.4 (2018): 2260-2268.
Chicago
Chen, Y., Ou, Y., Tao, Y., Liu, H., Yin, H., Zhong, S., Yu, H., Zhao, Z., He, B."Effect and mechanisms of celastrol on the apoptosis of HOS osteosarcoma cells". Oncology Reports 40, no. 4 (2018): 2260-2268. https://doi.org/10.3892/or.2018.6619