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Article

Cytotoxic effects of NF‑κB inhibitors in combination with anti‑herpes agents on Epstein‑Barr virus‑positive gastric carcinoma in vitro

  • Authors:
    • Paula Ordonez
    • Athira Nandakumar
    • Chihaya Koriyama
    • Megumi Yamomoto
    • Suminori Akiba
  • View Affiliations / Copyright

    Affiliations: Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan, Department of Basic Medical Sciences, National Institute for Minamata Disease, Minamata, Kumamoto 867‑0008, Japan
  • Pages: 2359-2367
    |
    Published online on: July 11, 2016
       https://doi.org/10.3892/mmr.2016.5496
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Abstract

Epstein-Barr virus (EBV) infection in tumor cells is usually restricted to the latent form, indicating that the induction of viral lytic infection may present a novel approach for the treatment of EBV‑associated tumors. By contrast, EBV lytic replication is inhibited by high‑levels of nuclear factor (NF)‑κB, which suggests that NF‑κB inhibitors may activate lytic replication from the latent form. In the current study, the addition of NF‑κB inhibitors (Bay11‑7082, Z‑LLF‑CHO and aspirin) was observed to induce the EBV lytic genes BZLF1, BRLF1 and BMRF1 in EBV‑positive gastric cancer (GC) cells. Both EBV‑positive and ‑negative GC cells were treated with different concentrations of anti‑herpes agents and the cytotoxic effects were measured at different time points following induction of EBV lytic replication. A marginal dose‑ and time‑dependent reduction in cell viability was observed for EBV‑positive and‑negative GC cells. The cytotoxic effects of NF‑κB inhibitors on EBV‑positive GC cells were enhanced by the addition of the anti‑herpes agents, ganciclovir, acyclovir, foscarnet and brivudine (P<0.05). However, there was no significant synergistic effect on EBV‑negative GC cells. The combination of 5 mM aspirin and ganciclovir exhibited the highest cytotoxic effect in EBV‑positive GC cells (CC50=7.2 µg/ml).
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1 

Adler B, Schaadt E, Kempkes B, Zimber-Strobl U, Baier B and Bornkamm GW: Control of Epstein-Barr virus reactivation by activated CD40 and viral latent membrane protein 1. Proc Natl Acad Sci USA. 99:437–442. 2002. View Article : Google Scholar

2 

Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O and Akira S: IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol. 6:981–988. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Brown HJ, Song MJ, Deng H, Wu TT, Cheng G and Sun R: NF-κB inhibits gammaherpesvirus lytic replication. J Virol. 77:8532–8540. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Kopp E and Ghosh S: Inhibition of NF-kappa B by sodium salicylate and aspirin. Science. 265:956–959. 1994. View Article : Google Scholar : PubMed/NCBI

5 

Yin MJ, Yamamoto Y and Gaynor RB: The anti-inflammatory agents aspirin and salicylate inhibit the activity of I (kappa)B kinase-beta. Nature. 396:77–80. 1998. View Article : Google Scholar : PubMed/NCBI

6 

Liu SF, Wang H, Li ZJ, Deng XY, Xiang H, Tao YG, Li W, Tang M and Cao Y: Aspirin induces lytic cytotoxicity in Epstein-Barr virus-positive cells. Eur J Pharmacol. 589:8–13. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Liu SF, Wang H, Lin XC, Xiang H, Deng XY, Li W, Tang M and Cao Y: NF-κB inhibitors induce lytic cytotoxicity in Epstein-Barr virus-positive nasopharyngeal carcinoma. Cell Biol Int. 32:1006–1013. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Visalli P and van Zeijl M: DNA encapsidation as a target for anti-herpesvirus drug therapy. Antiviral Res. 59:73–87. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Meng Q, Hagemeier SR, Fingeroth JD, Gershburg E, Pagano JS and Kenney SC: The Epstein-Barr virus (EBV)-encoded protein kinase, EBV-PK, but not the thymidine kinase (EBV-TK), is required for ganciclovir and acyclovir inhibition of lytic viral production. J Virol. 84:4534–4542. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Harris SA, McGuigan C, Andrei G, Snoeck R, De Clercq E and Balzarini J: Synthesis and antiviral evaluation of phosphoramidate derivatives of (E)-5-(2-bromovinyl)-2′-deoxyuridine. Antivir Chem Chemother. 12:293–300. 2001. View Article : Google Scholar

11 

Meyer PR, Rutvisuttinunt W, Matsuura SE, So AG and Scott WA: Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primer-template controlled by binding deoxynucleoside triphosphates or foscarnet. J Mol Biol. 369:41–54. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Burke AP, Yen TS, Shekitka KM and Sobin LH: Lymphoepithelial carcinoma of the stomach with Epstein-Barr virus demonstrated by polymerase chain reaction. Mod Pathol. 3:377–380. 1990.PubMed/NCBI

13 

Shibata D, Tokunaga M, Uemura Y, Sato E, Tanaka S and Weiss LM: Association of Epstein-Barr virus with undifferentiated gastric carcinomas with intense lymphoid infiltration lymphoepithelioma-like carcinoma. Am J Pathol. 139:469–447. 1991.PubMed/NCBI

14 

Takada K: Epstein-Barr virus and gastric carcinoma. Mol Pathol. 53:255–261. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Israel BF and Kenney SC: Virally targeted therapies for EBV-associated malignancies. Oncogene. 22:5122–5130. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Ji Jung E, Mie Lee Y, Lan Lee B, Soo Chang M and Ho Kim W: Ganciclovir augments the lytic induction and apoptosis induced by chemotherapeutic agents in an Epstein-Barr virus-infected gastric carcinoma cell line. Anticancer Drugs. 18:79–85. 2007.

17 

Ryan JL, Fan H, Glaser SL, Schichman SA, Raab-Traub N and Gulley ML: Epstein-Barr virus quantitation by real-time PCR and targeting multiple gene segments: A novel approach to screen for the virus in paraffin-embedded tissue and plasma. J Mol Diagn. 6:378–385. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Hilscher C, Vahrson W and Dittmer DP: Faster quantitative real-time PCR protocols may lose sensitivity and show increased variability. Nucleic Acids Res. 33:e1822005. View Article : Google Scholar : PubMed/NCBI

19 

Jeong JY, Woo JH, Kim YS, Choi S, Lee SO, Kil SR, Kim CW, Lee BL, Kim WH, Nam BH and Chang MS: Nuclear factor-kappa B inhibition reduces markedly cell proliferation in Epstein-Barr virus-infected stomach cancer, but affects variably in Epstein-Barr virus-negative stomach cancer. Cancer Invest. 28:113–119. 2010. View Article : Google Scholar

20 

Ding L, Li LL, Yang J, Tao YG, Ye M, Shi Y, Tang M, Yi W, Li XL, Gong JP and Cao Y: Epstein-Barr virus encoded latent membrane protein 1 modulates nuclear translocation of telomerase reverse transcriptase protein by activating nuclear factor-kappaB p65 in human nasopharyngeal carcinoma cells. Int J Biochem Cell Biol. 37:1881–1889. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Pierce JW, Schoenleber R, Jesmok G, Best J, Moore SA, Collins T and Gerritsen ME: Novel inhibitors of cytokine-induced IkappaBalpha phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo. J Biol Chem. 272:21096–21103. 1997. View Article : Google Scholar : PubMed/NCBI

22 

Sergerie Y and Boivin G: Evaluation of susceptibility of human herpesvirus 8 to antiviral drugs by quantitative real-time PCR. J Clin Microbiol. 41:3897–3900. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Westphal EM, Mauser A, Swenson J, Davis MG, Talarico CL and Kenney SC: Induction of lytic Epstein-Barr virus (EBV) infection in EBV-associated malignancies using adenovirus vectors in vitro and in vivo. Cancer Res. 59:1485–1491. 1999.PubMed/NCBI

24 

Takimoto T, Iwawaki J, Tanaka S and Umeda R: Interactions between Epstein-Barr virus (EBV) and human cell lines: Growth and EBV induction. ORL J Otorhinolaryngol Relat Spec. 52:40–46. 1990. View Article : Google Scholar : PubMed/NCBI

25 

Bren GD, Solan NJ, Miyoshi H, Pennington KN, Pobst LJ and Paya CV: Transcription of the RelB gene is regulated by NF-kappaB. Oncogene. 20:7722–7733. 2001. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ordonez P, Nandakumar A, Koriyama C, Yamomoto M and Akiba S: Cytotoxic effects of NF‑κB inhibitors in combination with anti‑herpes agents on Epstein‑Barr virus‑positive gastric carcinoma in vitro. Mol Med Rep 14: 2359-2367, 2016.
APA
Ordonez, P., Nandakumar, A., Koriyama, C., Yamomoto, M., & Akiba, S. (2016). Cytotoxic effects of NF‑κB inhibitors in combination with anti‑herpes agents on Epstein‑Barr virus‑positive gastric carcinoma in vitro. Molecular Medicine Reports, 14, 2359-2367. https://doi.org/10.3892/mmr.2016.5496
MLA
Ordonez, P., Nandakumar, A., Koriyama, C., Yamomoto, M., Akiba, S."Cytotoxic effects of NF‑κB inhibitors in combination with anti‑herpes agents on Epstein‑Barr virus‑positive gastric carcinoma in vitro". Molecular Medicine Reports 14.3 (2016): 2359-2367.
Chicago
Ordonez, P., Nandakumar, A., Koriyama, C., Yamomoto, M., Akiba, S."Cytotoxic effects of NF‑κB inhibitors in combination with anti‑herpes agents on Epstein‑Barr virus‑positive gastric carcinoma in vitro". Molecular Medicine Reports 14, no. 3 (2016): 2359-2367. https://doi.org/10.3892/mmr.2016.5496
Copy and paste a formatted citation
x
Spandidos Publications style
Ordonez P, Nandakumar A, Koriyama C, Yamomoto M and Akiba S: Cytotoxic effects of NF‑κB inhibitors in combination with anti‑herpes agents on Epstein‑Barr virus‑positive gastric carcinoma in vitro. Mol Med Rep 14: 2359-2367, 2016.
APA
Ordonez, P., Nandakumar, A., Koriyama, C., Yamomoto, M., & Akiba, S. (2016). Cytotoxic effects of NF‑κB inhibitors in combination with anti‑herpes agents on Epstein‑Barr virus‑positive gastric carcinoma in vitro. Molecular Medicine Reports, 14, 2359-2367. https://doi.org/10.3892/mmr.2016.5496
MLA
Ordonez, P., Nandakumar, A., Koriyama, C., Yamomoto, M., Akiba, S."Cytotoxic effects of NF‑κB inhibitors in combination with anti‑herpes agents on Epstein‑Barr virus‑positive gastric carcinoma in vitro". Molecular Medicine Reports 14.3 (2016): 2359-2367.
Chicago
Ordonez, P., Nandakumar, A., Koriyama, C., Yamomoto, M., Akiba, S."Cytotoxic effects of NF‑κB inhibitors in combination with anti‑herpes agents on Epstein‑Barr virus‑positive gastric carcinoma in vitro". Molecular Medicine Reports 14, no. 3 (2016): 2359-2367. https://doi.org/10.3892/mmr.2016.5496
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