Caspase‑dependent apoptotic death by gadolinium chloride (GdCl3) via reactive oxygen species production and MAPK signaling in rat C6 glioma cells

  • Authors:
    • Yuh‑Feng Tsai
    • Yuh‑Fung Chen
    • Chen‑Yu Hsiao
    • Ching‑Wen  Huang
    • Chi‑Cheng Lu
    • Shih‑Chang Tsai
    • Jai‑Sing Yang
  • View Affiliations

  • Published online on: December 7, 2018     https://doi.org/10.3892/or.2018.6913
  • Pages: 1324-1332
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Abstract

Gadolinium (Gd) compounds serve as magnetic resonance imaging contrast agents and exert certain anticancer activities. Yet, the molecular signaling underlying the antitumor effect of Gd chloride (GdCl3) on glioma remains unclear. In the present study, we aimed to ascertain the apoptotic mechanisms of GdCl3 on rat glioma C6 cells. Our results demonstrated that GdCl3 significantly reduced cell viability and shrunk cell morphology of C6 cells in a concentration‑dependent manner. GdCl3 led to apoptotic C6 cell death as detected by TUNEL staining. An increase in cleaved caspase‑3, cleaved caspase‑8 and cleaved caspase‑9 occurred in GdCl3‑treated C6 cells as detected by immunoblotting analysis. The activities of caspase‑3, caspase‑8 and caspase‑9 were increased, and the specific inhibitors of caspase‑3/‑8/‑9 individually reversed cell viability, which caused apoptotic death in C6 cells prior to GdCl3 exposure. GdCl3 also caused an elevation in the cytoplasmic Ca2+ level and reactive oxygen species (ROS) production, as well as the loss of mitochondrial membrane potential (ΔΨm) as shown by flow cytometric analysis in C6 cells. The results from the immunoblotting analysis demonstrated that there were upregulated protein levels of cytochrome c and Bax but a downregulated protein level of Bcl‑2 in C6 cells after GdCl3 treatment. Additionally, GdCl3 decreased the protein levels of phosphorylated‑extracellular signal‑regulated kinases, phosphorylated‑c‑Jun N‑terminal kinase and phosphorylated‑p38 mitogen‑activated protein kinases in C6 cells. In conclusion, ROS production and MAPKs signaling pathways contribute to GdCl3‑induced caspase cascade‑mediated apoptosis in C6 cells. Our findings provide a better understanding of the molecular mechanisms underlying the role of GdCl3 in rat glioma C6 cells.
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February-2019
Volume 41 Issue 2

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

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Spandidos Publications style
Tsai YF, Chen YF, Hsiao CY, Huang CW, Lu CC, Tsai SC and Yang JS: Caspase‑dependent apoptotic death by gadolinium chloride (GdCl3) via reactive oxygen species production and MAPK signaling in rat C6 glioma cells. Oncol Rep 41: 1324-1332, 2019.
APA
Tsai, Y., Chen, Y., Hsiao, C., Huang, C., Lu, C., Tsai, S., & Yang, J. (2019). Caspase‑dependent apoptotic death by gadolinium chloride (GdCl3) via reactive oxygen species production and MAPK signaling in rat C6 glioma cells. Oncology Reports, 41, 1324-1332. https://doi.org/10.3892/or.2018.6913
MLA
Tsai, Y., Chen, Y., Hsiao, C., Huang, C., Lu, C., Tsai, S., Yang, J."Caspase‑dependent apoptotic death by gadolinium chloride (GdCl3) via reactive oxygen species production and MAPK signaling in rat C6 glioma cells". Oncology Reports 41.2 (2019): 1324-1332.
Chicago
Tsai, Y., Chen, Y., Hsiao, C., Huang, C., Lu, C., Tsai, S., Yang, J."Caspase‑dependent apoptotic death by gadolinium chloride (GdCl3) via reactive oxygen species production and MAPK signaling in rat C6 glioma cells". Oncology Reports 41, no. 2 (2019): 1324-1332. https://doi.org/10.3892/or.2018.6913