CpG oligodeoxynucleotide induces apoptosis and cell cycle arrest in A20 lymphoma cells via TLR9-mediated pathways

Xu Feng Qi, Li Zheng, Cheol Su Kim, Kyu Jae Lee, Dong Heui Kim, Dong Qing Cai, Jun Wen Qin, Yan Hong Yu, Zheng Wu, Soo Ki Kim

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10 Citations (Scopus)

Abstract

Recent studies have suggested that the anti-cancer activity of CpG-oligodeoxynucleotides (CpG-ODNs) is owing to their immunomodulatory effects in tumor-bearing host. The purpose of this study is to investigate the directly cytotoxic activity of KSK-CpG, a novel CpG-ODN with an alternative CpG motif, against A20 and EL4 lymphoma cells in comparison with previously used murine CpG motif (1826-CpG). To evaluate the potential cytotoxic effects of KSK-CpG on lymphoma cells, cell viability assay, confocal microscopy, flow cytometry, DNA fragmentation, Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR) analysis were used. We found that KSK-CpG induced direct cytotoxicity in A20 lymphoma cells, but not in EL4 lymphoma cells, at least in part via TLR9-mediated pathways. Apoptotic cell death was demonstrated to play an important role in CpG-ODNs-induced cytotoxicity. In addition, both mitochondrial membrane potential decrease and G1-phase arrest were involved in KSK-CpG-induced apoptosis in A20 cells. The activities of apoptotic molecules such as caspase-3, PARP, and Bax were increased, but the activation of p27 Kip1 and ERK were decreased in KSK-CpG-treated A20 cells. Furthermore, autocrine IFN-γ partially contributed to apoptotic cell death in KSK-CpG-treated A20 cells. Collectively, our findings suggest that KSK-CpG induces apoptotic cell death in A20 lymphoma cells at least in part by inducing G1-phase arrest and autocrine IFN-γ via increasing TLR9 expression, without the need for immune system of tumor-bearing host. This new understanding supports the development of TLR9-targeted therapy with CpG-ODN as a direct therapeutic agent for treating B lymphoma.

Original languageEnglish
Pages (from-to)327-337
Number of pages11
JournalMolecular Immunology
Volume54
Issue number3-4
DOIs
Publication statusPublished - 2013 Jul

All Science Journal Classification (ASJC) codes

  • Immunology
  • Molecular Biology

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    Qi, X. F., Zheng, L., Kim, C. S., Lee, K. J., Kim, D. H., Cai, D. Q., Qin, J. W., Yu, Y. H., Wu, Z., & Kim, S. K. (2013). CpG oligodeoxynucleotide induces apoptosis and cell cycle arrest in A20 lymphoma cells via TLR9-mediated pathways. Molecular Immunology, 54(3-4), 327-337. https://doi.org/10.1016/j.molimm.2013.01.001