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Akbu-LAAO exhibits potent anti-tumor activity to HepG2 cells partially through produced H(2)O(2) via TGF-β signal pathway

Previously, we characterized the biological properties of Akbu-LAAO, a novel L-amino acid oxidase from Agkistrodon blomhoffii ussurensis snake venom (SV). Current work investigated its in vitro anti-tumor activity and underlying mechanism on HepG2 cells. Akbu-LAAO inhibited HepG2 growth time and dos...

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Autores principales: Guo, Chunmei, Liu, Shuqing, Dong, Panpan, Zhao, Dongting, Wang, Chengyi, Tao, Zhiwei, Sun, Ming-Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677388/
https://www.ncbi.nlm.nih.gov/pubmed/26655928
http://dx.doi.org/10.1038/srep18215
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author Guo, Chunmei
Liu, Shuqing
Dong, Panpan
Zhao, Dongting
Wang, Chengyi
Tao, Zhiwei
Sun, Ming-Zhong
author_facet Guo, Chunmei
Liu, Shuqing
Dong, Panpan
Zhao, Dongting
Wang, Chengyi
Tao, Zhiwei
Sun, Ming-Zhong
author_sort Guo, Chunmei
collection PubMed
description Previously, we characterized the biological properties of Akbu-LAAO, a novel L-amino acid oxidase from Agkistrodon blomhoffii ussurensis snake venom (SV). Current work investigated its in vitro anti-tumor activity and underlying mechanism on HepG2 cells. Akbu-LAAO inhibited HepG2 growth time and dose-dependently with an IC(50) of ~38.82 μg/mL. It could induce the apoptosis of HepG2 cells. Akbu-LAAO exhibited cytotoxicity by inhibiting growth and inducing apoptosis of HepG2 as it showed no effect on its cell cycle. The inhibition of Akbu-LAAO to HepG2 growth partially relied on enzymatic-released H(2)O(2) as catalase only partially antagonized this effect. cDNA microarray results indicated TGF-β signaling pathway was linked to the cytotoxicity of Akbu-LAAO on HepG2. TGF-β pathway related molecules CYR61, p53, GDF15, TOB1, BTG2, BMP2, BMP6, SMAD9, JUN, JUNB, LOX, CCND1, CDK6, GADD45A, CDKN1A were deregulated in HepG2 following Akbu-LAAO stimulation. The presence of catalase only slightly restored the mRNA changes induced by Akbu-LAAO for differentially expressed genes. Meanwhile, LDN-193189, a TGF-β pathway inhibitor reduced Akbu-LAAO cytotoxicity on HepG2. Collectively, we reported, for the first time, SV-LAAO showed anti-tumor cell activity via TGF-β pathway. It provides new insight of SV-LAAO exhibiting anti-tumor effect via a novel signaling pathway.
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spelling pubmed-46773882015-12-17 Akbu-LAAO exhibits potent anti-tumor activity to HepG2 cells partially through produced H(2)O(2) via TGF-β signal pathway Guo, Chunmei Liu, Shuqing Dong, Panpan Zhao, Dongting Wang, Chengyi Tao, Zhiwei Sun, Ming-Zhong Sci Rep Article Previously, we characterized the biological properties of Akbu-LAAO, a novel L-amino acid oxidase from Agkistrodon blomhoffii ussurensis snake venom (SV). Current work investigated its in vitro anti-tumor activity and underlying mechanism on HepG2 cells. Akbu-LAAO inhibited HepG2 growth time and dose-dependently with an IC(50) of ~38.82 μg/mL. It could induce the apoptosis of HepG2 cells. Akbu-LAAO exhibited cytotoxicity by inhibiting growth and inducing apoptosis of HepG2 as it showed no effect on its cell cycle. The inhibition of Akbu-LAAO to HepG2 growth partially relied on enzymatic-released H(2)O(2) as catalase only partially antagonized this effect. cDNA microarray results indicated TGF-β signaling pathway was linked to the cytotoxicity of Akbu-LAAO on HepG2. TGF-β pathway related molecules CYR61, p53, GDF15, TOB1, BTG2, BMP2, BMP6, SMAD9, JUN, JUNB, LOX, CCND1, CDK6, GADD45A, CDKN1A were deregulated in HepG2 following Akbu-LAAO stimulation. The presence of catalase only slightly restored the mRNA changes induced by Akbu-LAAO for differentially expressed genes. Meanwhile, LDN-193189, a TGF-β pathway inhibitor reduced Akbu-LAAO cytotoxicity on HepG2. Collectively, we reported, for the first time, SV-LAAO showed anti-tumor cell activity via TGF-β pathway. It provides new insight of SV-LAAO exhibiting anti-tumor effect via a novel signaling pathway. Nature Publishing Group 2015-12-14 /pmc/articles/PMC4677388/ /pubmed/26655928 http://dx.doi.org/10.1038/srep18215 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Guo, Chunmei
Liu, Shuqing
Dong, Panpan
Zhao, Dongting
Wang, Chengyi
Tao, Zhiwei
Sun, Ming-Zhong
Akbu-LAAO exhibits potent anti-tumor activity to HepG2 cells partially through produced H(2)O(2) via TGF-β signal pathway
title Akbu-LAAO exhibits potent anti-tumor activity to HepG2 cells partially through produced H(2)O(2) via TGF-β signal pathway
title_full Akbu-LAAO exhibits potent anti-tumor activity to HepG2 cells partially through produced H(2)O(2) via TGF-β signal pathway
title_fullStr Akbu-LAAO exhibits potent anti-tumor activity to HepG2 cells partially through produced H(2)O(2) via TGF-β signal pathway
title_full_unstemmed Akbu-LAAO exhibits potent anti-tumor activity to HepG2 cells partially through produced H(2)O(2) via TGF-β signal pathway
title_short Akbu-LAAO exhibits potent anti-tumor activity to HepG2 cells partially through produced H(2)O(2) via TGF-β signal pathway
title_sort akbu-laao exhibits potent anti-tumor activity to hepg2 cells partially through produced h(2)o(2) via tgf-β signal pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677388/
https://www.ncbi.nlm.nih.gov/pubmed/26655928
http://dx.doi.org/10.1038/srep18215
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