Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer

  • Authors:
    • Yoshiaki Sato
    • Hironori Yoshino
    • Yuka Kazama
    • Ikuo Kashiwakura
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  • Published online on: October 8, 2018     https://doi.org/10.3892/mmr.2018.9536
  • Pages: 5286-5294
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Abstract

Retinoic acid‑inducible gene‑I‑like receptors (RLRs) serve an important role in antiviral immune responses. Recent studies demonstrated that RLR activation exerts antitumor activity by inducing an anticancer immune response and apoptosis in various cancer cells. The authors' recent study demonstrated that the cytotoxic effects of the RLR agonist Poly(I:C)‑HMW/LyoVec™ [Poly(I:C)‑HMW] in human non‑small cell lung cancer (NSCLC) were enhanced by cotreatment with ionizing radiation (IR). Furthermore, cotreatment with Poly(I:C)‑HMW and IR effectively induced cell death, including apoptosis, in a caspase‑dependent manner. However, the mechanisms by which cotreatment with Poly(I:C)‑HMW and IR effectively induce apoptosis remains unclear. Therefore, the pathways involved in the increase in apoptosis elicited by cotreatment with Poly(I:C)‑HMW and IR in the A549 human NSCLC cell line were investigated. Poly(I:C)‑HMW induced the expression of active caspase‑8 and ‑9, and the Poly(I:C)‑HMW‑induced increase in the cell cycle sub‑G1 population, which is one of the hallmarks of apoptosis, was decreased by treatment with a caspase‑8 inhibitor and caspase‑9 inhibitor. When cells were treated with Poly(I:C)‑HMW and IR, the sub‑G1 population, and the active caspase‑8 and caspase‑9 expression were all increased compared with cells treated with Poly(I:C)‑HMW or IR alone. Furthermore, expression of X‑linked inhibitor of apoptosis protein, which negatively regulates caspase activation, was decreased in cells cotreated with Poly(I:C)‑HMW and IR. Notably, treatment with an inhibitor for caspase‑8, not caspase‑9, partially reversed the net increase in the sub‑G1 population induced by cotreatment with Poly(I:C)‑HMW and IR. Collectively, these results suggested that Poly(I:C)‑HMW induces apoptosis through caspase‑8 and caspase‑9 activation; however, the apoptotic pathway mediated by casapse‑8, and not casapse‑9, is involved in the enhancement of apoptosis caused by cotreatment with Poly(I:C)‑HMW and IR.
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December-2018
Volume 18 Issue 6

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

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Spandidos Publications style
Sato Y, Yoshino H, Kazama Y and Kashiwakura I: Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer. Mol Med Rep 18: 5286-5294, 2018
APA
Sato, Y., Yoshino, H., Kazama, Y., & Kashiwakura, I. (2018). Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer. Molecular Medicine Reports, 18, 5286-5294. https://doi.org/10.3892/mmr.2018.9536
MLA
Sato, Y., Yoshino, H., Kazama, Y., Kashiwakura, I."Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer". Molecular Medicine Reports 18.6 (2018): 5286-5294.
Chicago
Sato, Y., Yoshino, H., Kazama, Y., Kashiwakura, I."Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer". Molecular Medicine Reports 18, no. 6 (2018): 5286-5294. https://doi.org/10.3892/mmr.2018.9536