Juglone potentiates TRAIL‑induced apoptosis in human melanoma cells via activating the ROS‑p38‑p53 pathway

  • Authors:
    • Xiao Liu
    • Yan Chen
    • Yaohua Zhang
    • Juan Du
    • Yubao Lv
    • Shuming Mo
    • Yingchao Liu
    • Feng Ding
    • Jinfeng Wu
    • Ji Li
  • View Affiliations

  • Published online on: October 17, 2017     https://doi.org/10.3892/mmr.2017.7806
  • Pages: 9645-9651
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Abstract

Tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL)‑based cancer therapy offers promise as TRAIL can kill cancer cells without apparent toxicity towards normal cells. However, intrinsic or acquired resistance to TRAIL inseveral types of cancer cell has become a major challenge in TRAIL‑based cancer therapy. Juglone is a natural compound isolated from walnut trees. In the present study, it was demonstrated that juglone sensitized melanoma cells to TRAIL‑induced cytotoxicity by MTT and crystal violet assays. Flow cytometry analysis indicated that juglone potentiated TRAIL‑induced cell death. Western blot assay demonstrated that the expressions of cleaved poly(ADP‑ribose) polymerase (PARP) and cleaved caspase 3 were markedly increased in the juglone combined with TRAIL group. Exposure to TRAIL alone did not induce the production of reactive oxygen species (ROS), activation of p38 orincrease of p53 in the TRAIL‑resistant melanoma cells, as determined by flow cytometry and western blot analysis. However, exposure to TRAIL in combination with juglone markedly increased the production of ROS, activated p38 and increased p53, compared with the cells treated with either juglone or TRAIL alone. Pretreatment with N‑acetyl cysteine, a ROS scavenger, significantly reduced the cytotoxicity of juglone in combination with TRAIL, which further supported that ROS was involved in the juglone‑induced sensitization of TRAIL. In conclusion, juglone potentiated TRAIL‑induced apoptosis in melanoma cells, and these effects were partially mediated through the ROS‑p38‑p53 pathway. These findings suggested that juglone may be a potential sensitizer for TRAIL therapy in the treatment of melanoma.
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December-2017
Volume 16 Issue 6

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

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Spandidos Publications style
Liu X, Chen Y, Zhang Y, Du J, Lv Y, Mo S, Liu Y, Ding F, Wu J, Li J, Li J, et al: Juglone potentiates TRAIL‑induced apoptosis in human melanoma cells via activating the ROS‑p38‑p53 pathway. Mol Med Rep 16: 9645-9651, 2017
APA
Liu, X., Chen, Y., Zhang, Y., Du, J., Lv, Y., Mo, S. ... Li, J. (2017). Juglone potentiates TRAIL‑induced apoptosis in human melanoma cells via activating the ROS‑p38‑p53 pathway. Molecular Medicine Reports, 16, 9645-9651. https://doi.org/10.3892/mmr.2017.7806
MLA
Liu, X., Chen, Y., Zhang, Y., Du, J., Lv, Y., Mo, S., Liu, Y., Ding, F., Wu, J., Li, J."Juglone potentiates TRAIL‑induced apoptosis in human melanoma cells via activating the ROS‑p38‑p53 pathway". Molecular Medicine Reports 16.6 (2017): 9645-9651.
Chicago
Liu, X., Chen, Y., Zhang, Y., Du, J., Lv, Y., Mo, S., Liu, Y., Ding, F., Wu, J., Li, J."Juglone potentiates TRAIL‑induced apoptosis in human melanoma cells via activating the ROS‑p38‑p53 pathway". Molecular Medicine Reports 16, no. 6 (2017): 9645-9651. https://doi.org/10.3892/mmr.2017.7806