NF-kappaB inhibitors induce lytic cytotoxicity in Epstein-Barr virus-positive nasopharyngeal carcinoma cells.
Epstein-Barr virus (EBV) infection in tumor cells is generally restricted to the latent forms of viral infection. Switching the latent form of viral infection into the lytic form may induce tumor cell death. An important nuclear factor, nuclear factor (NF)-kappaB, is thought to play an essential role in EBV lytic infection; high levels of NF-kappaB can inhibit EBV lytic replication. In this study, we tested the effect of inducing EBV lytic replication using two NF-kappaB inhibitors: Bay11-7082 and Z-LLF-CHO, to reveal the possibility of targeting EBV-positive cancer therapy with these two NF-kappaB inhibitors. Our results showed that Bay11-7082 and Z-LLF-CHO reactivated EBV in a dose-dependent manner, thus resulting in EBV-positive 5-8F cell death. In contrast, there was no significant effect on EBV-negative HNE3 cells. When ganciclovir was used in combination with either Bay11-7082 or Z-LLF-CHO to treat 5-8F cells, the cytotoxic effect of the NF-kappaB inhibitor was amplified. The finding indicates that inhibiting the NF-kappaB activity of EBV-positive cells can induce lytic replication of EBV and cause lytic cytotoxicity against these cells.
Liu
Su-Fang
SF
Cancer Research Institute, Xiangya School of Medicine, Central South University, and Medicine Experimental Center, The Third Xiangya Hospital, Changsha, 410078 Hunan, PR China.
Wang
Hai
H
Lin
Xu-Chi
XC
Xiang
Hui
H
Deng
Xi-Yun
XY
Li
Wei
W
Tang
Min
M
Cao
Ya
Y
D000998:Antiviral Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000378:metabolism / Q000821:virology*; D015774:Ganciclovir / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D009570:Nitriles / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism; D014775:Virus Activation
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000998:Antiviral Agents; D016328:NF-kappa B; D009570:Nitriles; D009842:Oligopeptides; D013450:Sulfones; D051996:Transcription Factor RelA; C077180:N-benzyloxycarbonyl-leucyl-leucyl-phenylalaninal; D015774:Ganciclovir