RT Journal Article SR Electronic T1 Branched Chain Amino Acid Suppressed Insulin-initiated Proliferation of Human Cancer Cells Through Induction of Autophagy JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 4789 OP 4796 VO 34 IS 9 A1 GIZACHEW YISMAW WUBETU A1 TOHRU UTSUNOMIYA A1 DAICHI ISHIKAWA A1 TETSUYA IKEMOTO A1 SHINICHIRO YAMADA A1 YUJI MORINE A1 SHUICHI IWAHASHI A1 YU SAITO A1 YUSUKE ARAKAWA A1 SATORU IMURA A1 HIDEKI ARIMOCHI A1 MITSUO SHIMADA YR 2014 UL http://ar.iiarjournals.org/content/34/9/4789.abstract AB 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. Materials and 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). Conclusion: BCAA could be a useful chemopreventive modality for cancer in hyperinsulinemic conditions.