title: Epigallocatechin gallate inhibits sphere formation of neuroblastoma BE(2)-C cells.
abstract: OBJECTIVE
  A growing number of epidemiological studies have demonstrated that the consumption of green tea inhibits the growth of a variety of cancers. Epigallocatechin gallate (EGCG), the most abundant catechin in green tea, has been shown to have an anti-cancer effect against many cancers. Most cancers are believed to be initiated from and maintained by a small population of tumor-initiating cells (TICs) that are responsible for chemotherapeutic resistance and tumor relapse. In neuroblastoma, an aggressive pediatric tumor that often relapses and has a poor prognosis, TICs were recently identified as spheres grown in a serum-free non-adherent culture used for neural crest stem cell growth. Although EGCG has been reported to induce growth arrest and apoptosis in neuroblastoma cells, its effect on neuroblastoma TICs remains to be defined.
  
  
  METHODS
  Gene expression was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). The effects of EGCG on cell proliferation, apoptosis, and sphere formation were determined by cell counting, propidium iodide staining, and sphere (>100 μm in diameter) counting, respectively.
  
  
  RESULTS
  Neuroblastoma BE(2)-C cells showed increased expression of stem cell markers (nanog homeobox [NANOG] and octamer-binding transcription factor 4 [OCT4]), as well as decreased expression of neuronal differentiation markers (Cu(2+)-transporting ATPase alpha polypeptide [ATP7A] and dickkopf homolog 2 [DKK2]) in spheres grown in serum-free non-adherent culture, compared to parental cells grown in conventional culture. Although EGCG induced growth arrest and apoptosis in the parental cells in a dose-dependent manner, it was not effective against spheres. However, EGCG potently inhibited sphere formation in the BE(2)-C cells.
  
  
  CONCLUSIONS
  The present results suggest that EGCG may inhibit the development of TICs in BE(2)-C cells.
authors: Department of Epidemiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Japan. nnishi@med.kobe-u.ac.jp
authors: Noriyuki
authors: N
authors: Nishimura
authors: Tri Budi
authors: TB
authors: Hartomo
authors: Thi Van Huyen
authors: TV
authors: Pham
authors: Myeong Jin
authors: MJ
authors: Lee
authors: Tomoto
authors: T
authors: Yamamoto
authors: Satoru
authors: S
authors: Morikawa
authors: Daiichiro
authors: D
authors: Hasegawa
authors: Hiroki
authors: H
authors: Takeda
authors: Keiichiro
authors: K
authors: Kawasaki
authors: Yoshiyuki
authors: Y
authors: Kosaka
authors: Nobuyuki
authors: N
authors: Yamamoto
authors: Ikuko
authors: I
authors: Kubokawa
authors: Takeshi
authors: T
authors: Mori
authors: Tomoko
authors: T
authors: Yanai
authors: Akira
authors: A
authors: Hayakawa
authors: Yasuhiro
authors: Y
authors: Takeshima
authors: Kazumoto
authors: K
authors: Iijima
authors: Masafumi
authors: M
authors: Matsuo
authors: Hisahide
authors: H
authors: Nishio
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009447:Neuroblastoma; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016588:Anticarcinogenic Agents; D002392:Catechin; C045651:epigallocatechin gallate