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.

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.

• Authors: Gizachew Yismaw Wubetu, Tohru Utsunomiya, Daichi Ishikawa, Tetsuya Ikemoto, Shinichiro Yamada, Yuji Morine, Shuichi Iwahashi, Yu Saito, Yusuke Arakawa, Satoru Imura, Hideki Arimochi, Mitsuo Shimada
• Journal: Anticancer research (Anticancer Res) Vol. 34 Issue 9 Pg. 4789-96 (Sep 2014) ISSN: 1791-7530 [Electronic] Greece
• PMID: 25202059 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Amino Acids, Branched-Chain
• Insulin
• Receptor, IGF Type 1

Topics

• Amino Acids, Branched-Chain (pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dietary Supplements
• HCT116 Cells
• Hep G2 Cells
• Humans
• Insulin (pharmacology)
• Phosphorylation (drug effects)
• Receptor, IGF Type 1 (metabolism)