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

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


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
Issue number3-4
Publication statusPublished - 2013 Jul

Bibliographical note

Funding Information:
This work was supported in part by National Natural Science Foundation of China ( 81100079 , 81270183 , 81211140351 ), Guangdong Natural Science Foundation ( S2011040003230 ), Fundamental Research Funds for the Central Universities (Ji Nan University) ( 21611301 , 21612410 , 21612356 ), Foundation for Distinguished Young Talents in Higher Education of Guangdong (34311007) , and Research Foundation for Recruitment Talents of Ji Nan University (50624058) , China.

All Science Journal Classification (ASJC) codes

  • Immunology
  • Molecular Biology


Dive into the research topics of 'CpG oligodeoxynucleotide induces apoptosis and cell cycle arrest in A20 lymphoma cells via TLR9-mediated pathways'. Together they form a unique fingerprint.

Cite this