Neddylation inhibitor MLN4924 induces G2 cell cycle arrest, DNA damage and sensitizes esophageal squamous cell carcinoma cells to cisplatin

  • Authors:
    • Shan Lin
    • Zhaoyang Shang
    • Shuo Li
    • Peng Gao
    • Yi Zhang
    • Shuaiheng Hou
    • Peng Qin
    • Ziming Dong
    • Tao Hu
    • Ping Chen
  • View Affiliations

  • Published online on: December 14, 2017     https://doi.org/10.3892/ol.2017.7616
  • Pages:2583-2589
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Abstract

Inhibiting the protein neddylation pathway using the NEDD8‑activating enzyme inhibitor MLN4924 represents an attractive anticancer strategy having been demonstrated to exhibit promising anticancer efficacy and with tolerable levels of toxicity; however, the mechanism by which MLN4924 inhibits cell proliferation in human esophageal squamous cell carcinoma (ESCC) cells requires further investigation. The present study revealed that MLN4924 treatment led to G2 cell cycle arrest and enhanced the protein stability of Wee1‑like protein kinase and cyclin dependent protein kinase inhibitor 1A and B and p27. Furthermore, MLN4924 induced DNA damage and sensitized esophageal cancer cells to cisplatin by enhancing apoptosis. These findings extend the understanding of the function and mechanism of MLN4924 in ESCC and provide further evidence for the future development of neddylation inhibitors in clinical trials of esophageal cancer therapy, either alone or in combination.

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February 2018
Volume 15 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Lin, S., Shang, Z., Li, S., Gao, P., Zhang, Y., Hou, S. ... Chen, P. (2018). Neddylation inhibitor MLN4924 induces G2 cell cycle arrest, DNA damage and sensitizes esophageal squamous cell carcinoma cells to cisplatin. Oncology Letters, 15, 2583-2589. https://doi.org/10.3892/ol.2017.7616
MLA
Lin, S., Shang, Z., Li, S., Gao, P., Zhang, Y., Hou, S., Qin, P., Dong, Z., Hu, T., Chen, P."Neddylation inhibitor MLN4924 induces G2 cell cycle arrest, DNA damage and sensitizes esophageal squamous cell carcinoma cells to cisplatin". Oncology Letters 15.2 (2018): 2583-2589.
Chicago
Lin, S., Shang, Z., Li, S., Gao, P., Zhang, Y., Hou, S., Qin, P., Dong, Z., Hu, T., Chen, P."Neddylation inhibitor MLN4924 induces G2 cell cycle arrest, DNA damage and sensitizes esophageal squamous cell carcinoma cells to cisplatin". Oncology Letters 15, no. 2 (2018): 2583-2589. https://doi.org/10.3892/ol.2017.7616