title: EGCG inhibits proliferation, invasiveness and tumor growth by up-regulation of adhesion molecules, suppression of gelatinases activity, and induction of apoptosis in nasopharyngeal carcinoma cells.
abstract: (-)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, has been shown to inhibit the proliferation of a variety of tumor cells. Epidemiological studies have shown that drinking green tea can reduce the incidence of nasopharyngeal carcinoma (NPC), yet the underlying mechanism is not well understood. In this study, the inhibitory effect of EGCG was tested on a set of Epstein Barr virus-negative and -positive NPC cell lines. Treatment with EGCG inhibited the proliferation of NPC cells but did not affect the growth of a non-malignant nasopharyngeal cell line, NP460hTert. Moreover, EGCG treated cells had reduced migration and invasive properties. The expression of the cell adhesion molecules E-cadherin and β-catenin was found to be up-regulated by EGCG treatment, while the down-regulation of matrix metalloproteinases (MMP)-2 and MMP-9 were found to be mediated by suppression of extracellular signal-regulated kinase (ERK) phosphorylation and AP-1 and Sp1 transactivation. Spheroid formation by NPC cells in suspension was significantly inhibited by EGCG. Oral administration of EGCG was capable of suppressing tumor growth in xenografted mice bearing NPC tumors. Treatment with EGCG was found to elevate the expression of p53 and p21, and eventually led to apoptosis of NPC cells via caspase 3 activation. The nuclear translocation of NF-κB and β-catenin was also suppressed by EGCG treatment. These results indicate that EGCG can inhibit the proliferation and invasiveness, and induce apoptosis, of NPC cells, making it a promising agent for chemoprevention or adjuvant therapy of NPC.
authors.affiliation: Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan. phildts@gmail.com.
authors.forename: Chih-Yeu
authors.initials: CY
authors.lastname: Fang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan Town, Miaoli County 350, Taiwan. chungcwu@nhri.org.tw.
authors.forename: Chung-Chun
authors.initials: CC
authors.lastname: Wu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan Town, Miaoli County 350, Taiwan. kakacoco0218@gmail.com.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Hsu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan Town, Miaoli County 350, Taiwan. tw.hitomi@gmail.com.
authors.forename: Hsin-Ying
authors.initials: HY
authors.lastname: Chuang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan Town, Miaoli County 350, Taiwan. syhuang@nhri.org.tw.
authors.forename: Sheng-Yen
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Department of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan. chtsai@ntu.edu.tw.
authors.forename: Ching-Hwa
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 701, Taiwan. yaochang@nhri.org.tw.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. gswtsao@hkucc.hku.hk.
authors.forename: George Sai-Wah
authors.initials: GS
authors.lastname: Tsao
authors.affiliation: Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan. chencl@tmu.edu.tw.
authors.forename: Chi-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan Town, Miaoli County 350, Taiwan. cjy@nhri.org.tw.
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma; D053148:Caspase 3 / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D016328:NF-kappa B / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D018874:Spheroids, Cellular / Q000187:drug effects; D014183:Transplantation, Heterologous; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D016328:NF-kappa B; D002392:Catechin; C045651:epigallocatechin gallate; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D018093:Gelatinases