TY - JOUR T1 - Branched Chain Amino Acid Suppressed Insulin-initiated Proliferation of Human Cancer Cells Through Induction of Autophagy JF - Anticancer Research JO - Anticancer Res SP - 4789 LP - 4796 VL - 34 IS - 9 AU - GIZACHEW YISMAW WUBETU AU - TOHRU UTSUNOMIYA AU - DAICHI ISHIKAWA AU - TETSUYA IKEMOTO AU - SHINICHIRO YAMADA AU - YUJI MORINE AU - SHUICHI IWAHASHI AU - YU SAITO AU - YUSUKE ARAKAWA AU - SATORU IMURA AU - HIDEKI ARIMOCHI AU - MITSUO SHIMADA Y1 - 2014/09/01 UR - http://ar.iiarjournals.org/content/34/9/4789.abstract N2 - 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. ER -