The STAT-ROS cycle extends IFN‑induced cancer cell apoptosis

  • Authors:
    • Yan Wang
    • Xiaoyu Yu
    • Hongtao Song
    • Di Feng
    • Yang Jiang
    • Shuang Wu
    • Jingshu Geng
  • View Affiliations

  • Published online on: November 8, 2017     https://doi.org/10.3892/ijo.2017.4196
  • Pages:305-313
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Abstract

In mammals, the signal transducer and activator of transcription (STAT) protein processes mitochondria importation targets and mitochondria respiratory complexes, and triggers reactive oxygen species (ROS) generation, which conversely rapidly initiates the activation of STAT. Interferon (IFN) administration increases cancer cell apoptosis via STAT activation and ROS accumulation. However, the existence of a STAT-ROS cycle and how it affects IFN‑induced cancer cellular apoptosis are unclear. In the present study, we used MCF7 breast cancer cells and confirmed that a combination of IFN‑α/β/γ incubation induced STAT1/3 phosphorylation and mitochondria importation, which increased mitochondria respiratory complexes, the cellular oxygen consumption rate (OCR), and ROS production, followed by cellular apoptosis. We also found that STAT1/3 overexpression induced mitochondria respiratory complexes and ROS production. Additionally, ROS induced by H2O2 induced phosphorylation of STAT1/3 and promoted mitochondria importation. STAT1/3 deletion suppressed H2O2-induced acute cellular OCR, increasing the ROS level and indicating that STAT1/3 is necessary for ROS-induced mitochondria OCR and further ROS production, suggesting the existence of a STAT-ROS cycle. We next found that IFN induced mitochondria respiratory complexes followed by induction of OCR, ROS, and apoptosis, which were partially blocked by STAT1/3 deletion. Additionally, the suppression of ROS inhibited IFN‑induced STAT1/3 activation. Finally, we discovered that this cycle exists also in A431 and HeLa cancer cells. These results indicate that a STAT-ROS cycle extends IFN‑induced cellular apoptosis.

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January 2018
Volume 52 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
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APA
Wang, Y., Yu, X., Song, H., Feng, D., Jiang, Y., Wu, S., & Geng, J. (2018). The STAT-ROS cycle extends IFN‑induced cancer cell apoptosis. International Journal of Oncology, 52, 305-313. https://doi.org/10.3892/ijo.2017.4196
MLA
Wang, Y., Yu, X., Song, H., Feng, D., Jiang, Y., Wu, S., Geng, J."The STAT-ROS cycle extends IFN‑induced cancer cell apoptosis". International Journal of Oncology 52.1 (2018): 305-313.
Chicago
Wang, Y., Yu, X., Song, H., Feng, D., Jiang, Y., Wu, S., Geng, J."The STAT-ROS cycle extends IFN‑induced cancer cell apoptosis". International Journal of Oncology 52, no. 1 (2018): 305-313. https://doi.org/10.3892/ijo.2017.4196