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Tumor Biology
Published in: Tumor Biology 11/2016

01-11-2016 | Original Article

γ-Aminobutyric acid inhibits the proliferation and increases oxaliplatin sensitivity in human colon cancer cells

Authors: Lihua Song, Aiying Du, Ying Xiong, Jing Jiang, Yao Zhang, Zhaofeng Tian, Hongli Yan

Published in: Tumor Biology | Issue 11/2016

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Abstract

γ-Aminobutyric acid (GABA) is a natural non-protein amino acid, which broadly exists in many plant parts and is widely used as an ingredient in the food industry. In mammals, it is widely distributed in central nervous system and non-neural tissues. In addition to a primary inhibitory neurotransmitter in the central nervous system, endogenous GABA content has been found to be elevated in neoplastic tissues in colon cancer. However, the effect of extraneous GABA on colon cancer has rarely been reported. In this study, we found the inhibitory effects of GABA on the proliferation of colon cancer cells (CCCs). The amino acid also suppressed metastasis of SW480 and SW620 cells. To further study the correlated mechanism, we analyzed the changes in cell cycle distribution and found that GABA suppressed cell cycle progression through G2/M or G1/S phase. Furthermore, RNA sequencing analysis revealed GABA-induced changes in the mRNA expression of 30 genes, including EGR1, MAPK4, NR4A1, Fos, and FosB, in all the three types of CCC. Importantly, GABA enhanced the anti-tumor efficacy of oxaliplatin (OXA) in subcutaneous xenograft tumor model in nude mice. The data suggest that GABA inhibits colon cancer cell proliferation perhaps by attenuating EGR1-NR4A1 axis, EGR1-Fos axis, and by disrupting MEK-EGR1 signaling pathway. This work reveals the pharmacological value of GABA derived from food and suggests that exogenous GABA might play an auxiliary role in polychemotherapy of colon cancer.
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Metadata
Title
γ-Aminobutyric acid inhibits the proliferation and increases oxaliplatin sensitivity in human colon cancer cells
Authors
Lihua Song
Aiying Du
Ying Xiong
Jing Jiang
Yao Zhang
Zhaofeng Tian
Hongli Yan
Publication date
01-11-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 11/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5367-5

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