title: Branched chain amino acid suppressed insulin-initiated proliferation of human cancer cells through induction of autophagy.
abstract: BACKGROUND
  Branched chain amino acid (BCAA) dietary supplementation inhibits activation of the insulin-like growth factor (IGF)/IGF-I receptor (IGF-IR) axis in diabetic animal models. However, the in vitro effect of BCAA on human cancer cell lines under hyper-insulinemic conditions remains unclear.
  
  
  METHODS
  Colon (HCT-116) and hepatic (HepG2) tumor cells were treated with varying concentrations of BCAA with or without fluorouracil (5-FU). The effect of BCAA on insulin-initiated proliferation was determined. Gene and protein expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively.
  
  
  RESULTS
  BCAA supplementation had no significant effect on cell proliferation and did not show significant synergistic or antagonistic effects with 5-FU. However, BCAA significantly decreased insulin-initiated proliferation of human colon and hepatic cancer cell lines in vitro. BCAA supplementation caused a marked decrease in activated IGF-IR expression and significantly enhanced both mRNA and protein expression of LC3-II and BECN1 (BECLIN-1).
  
  
  CONCLUSIONS
  BCAA could be a useful chemopreventive modality for cancer in hyperinsulinemic conditions.
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Gizachew Yismaw
authors.initials: GY
authors.lastname: Wubetu
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Utsunomiya
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: Tetsuya
authors.initials: T
authors.lastname: Ikemoto
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: Yuji
authors.initials: Y
authors.lastname: Morine
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: 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
authors.affiliation: Department of Immunology and Parasitology, The University of Tokushima, Tokushima, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Arimochi
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan mitsuo.shimada@tokushima-u.ac.jp.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000378:metabolism
chemical_list: D000597:Amino Acids, Branched-Chain; D007328:Insulin; D017526:Receptor, IGF Type 1
keywords: Autophagy; BCAA; colorectal cancer; insulin; liver cancer