title: EBV reactivation as a target of luteolin to repress NPC tumorigenesis.
abstract: Nasopharyngeal carcinoma (NPC) is a malignancy derived from the epithelial cells of the nasopharynx. Although a combination of radiotherapy with chemotherapy is effective for therapy, relapse and metastasis after remission remain major causes of mortality. Epstein-Barr virus (EBV) is believed to be one of causes of NPC development. We demonstrated previously that EBV reactivation is important for the carcinogenesis of NPC. We sought, therefore, to determine whether EBV reactivation can be a target for retardation of relapse of NPC. After screening, we found luteolin is able to inhibit EBV reactivation. It inhibited EBV lytic protein expression and repressed the promoter activities of two major immediate-early genes, Zta and Rta. Furthermore, luteolin was shown to reduce genomic instability induced by recurrent EBV reactivation in NPC cells. EBV reactivation-induced NPC cell proliferation and migration, as well as matrigel invasiveness, were also repressed by luteolin treatment. Tumorigenicity in mice, induced by EBV reactivation, was decreased profoundly following luteolin administration. Together, these results suggest that inhibition of EBV reactivation is a novel approach to prevent the relapse of NPC.
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Chung-Chun
authors.initials: CC
authors.lastname: Wu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.|Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chih-Yeu
authors.initials: CY
authors.lastname: Fang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Hsu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Hsin-Ying
authors.initials: HY
authors.lastname: Chuang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yu-Jhen
authors.initials: YJ
authors.lastname: Cheng
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yen-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Chou
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Sheng-Yen
authors.initials: SY
authors.lastname: Huang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Lin
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ching-Hwa
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.|Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Chen
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D002277:Carcinoma; D045744:Cell Line, Tumor; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy / Q000235:genetics / Q000821:virology; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D047311:Luteolin / Q000494:pharmacology*; D051379:Mice; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000821:virology*; D015534:Trans-Activators / Q000235:genetics; D014775:Virus Activation / Q000187:drug effects*
chemical_list: C068382:BRLF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D047311:Luteolin
keywords: Epstein-Barr virus; luteolin; nasopharyngeal carcinoma; reactivation; relapse