title: Epigallocatechin gallate hinders human hepatoma and colon cancer sphere formation.
abstract: OBJECTIVE
  The long-term survival of patients with hepatocellular carcinoma remains unsatisfactory because of the presence of cancer stem cells (CSCs), which are responsible for tumor recurrence and chemoresistance after hepatectomy. Drugs that selectively target CSCs thus offer great promise for cancer treatment. Although the antitumor effects of epigallocatechin gallate (EGCG) have been reported in some cancer cells, its effects on CSCs remain poorly studied. In this study, we investigated the effects of EGCG on human hepatoma and colon CSCs.
  
  
  METHODS
  HepG2 and HCT-116 cell lines were enriched by sphere formation, and their gene-expression profiles were analyzed by quantitative real-time polymerase chain reaction. EGCG-induced growth inhibition in the parental cells was determined by WST-8 assay, and protein expression was assessed by western blotting. Cell cycle profile and apoptosis analysis was performed using flow cytometer.
  
  
  RESULTS
  Sphere-derived cells grown in serum-free, nonadherent cultures showed increased expression of stem cell markers, Nek2, and ATP-binding cassette transporter genes, compared with parental cells grown in conventional culture. EGCG induced growth inhibition in the parental cells in a dose-dependent manner. EGCG also inhibited self-renewal in hepatoma and colon CSCs, attenuated the expression of stem cell markers and ATP-binding cassette transporter genes, which are putative molecules associated with treatment resistance in CSCs, and decreased the transcription of Nek2 and p-Akt, resulting in the inhibition of Akt signaling. EGCG also altered cell cycle profile and apoptosis, which may in part play an important role in EGCG-induced cancer cell death.
  
  
  CONCLUSIONS
  Overall, these results suggest that EGCG could be a useful chemopreventive agent for targeting hepatocellular carcinoma and colon CSCs, in combination with standard chemotherapies.
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Gizachew Y
authors.initials: GY
authors.lastname: Wubetu
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morine
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikemoto
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Ishikawa
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Iwahashi
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Arakawa
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Imura
mesh_terms: D000972:Antineoplastic Agents, Phytogenic; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology; D013662:Tea
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate
keywords: cancer sphere; cancer stem cell; colon; epigallocatechin gallate; hepatoma