Open Access

Aurora kinase A inhibitor TCS7010 demonstrates pro‑apoptotic effect through the unfolded protein response pathway in HCT116 colon cancer cells

  • Authors:
    • Da Hyun Lee
    • Chang Gun Kim
    • Yoongho Lim
    • Soon Young Shin
  • View Affiliations

  • Published online on: September 22, 2017     https://doi.org/10.3892/ol.2017.7023
  • Pages:6571-6577
  • Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aurora kinase A (AURKA) is essential for regulating mitosis and is frequently amplified in various cancer cell types. However, the effect of AURKA inhibition on the induction of apoptosis remains unclear. In the present study, it was reported that treatment with TCS7010, a specific inhibitor of AURKA, resulted in the accumulation of cells in the sub‑G0/G1 phase of the cell cycle and increased the percentage of annexin V‑binding cells. The cleavage of caspase‑2, caspase‑7, and poly(ADP‑ribose)polymerase (PARP) significantly increased in a time‑dependent manner following TCS7010 treatment. In addition, TCS7010 resulted in the production of reactive oxygen species (ROS) and stimulation of the unfolded protein response (UPR), leading to the upregulation of CCAAT/enhancer‑binding protein‑homologous protein (CHOP), and its downstream target BCL2 like 11 (BIM). Pretreatment with N‑acetylcystein, a ROS scavenger, significantly abrogated TCS7010‑induced accumulation of CHOP, BIM, cleaved caspase‑7 and cleaved PARP. These results suggest that TCS7010 triggers apoptosis through the ROS‑mediated UPR signaling pathway.

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December 2017
Volume 14 Issue 6

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

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Lee, D.H., Kim, C.G., Lim, Y., & Shin, S.Y. (2017). Aurora kinase A inhibitor TCS7010 demonstrates pro‑apoptotic effect through the unfolded protein response pathway in HCT116 colon cancer cells. Oncology Letters, 14, 6571-6577. https://doi.org/10.3892/ol.2017.7023
MLA
Lee, D. H., Kim, C. G., Lim, Y., Shin, S. Y."Aurora kinase A inhibitor TCS7010 demonstrates pro‑apoptotic effect through the unfolded protein response pathway in HCT116 colon cancer cells". Oncology Letters 14.6 (2017): 6571-6577.
Chicago
Lee, D. H., Kim, C. G., Lim, Y., Shin, S. Y."Aurora kinase A inhibitor TCS7010 demonstrates pro‑apoptotic effect through the unfolded protein response pathway in HCT116 colon cancer cells". Oncology Letters 14, no. 6 (2017): 6571-6577. https://doi.org/10.3892/ol.2017.7023