title: Akbu-LAAO exhibits potent anti-tumor activity to HepG2 cells partially through produced H2O2 via TGF-β signal pathway.
abstract: 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 IC50 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 H2O2 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.
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Biochemistry, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Shuqing
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, 116044, China.|Department of Biochemistry, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Dong
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, 116044, China.|Department of Biochemistry, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Dongting
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, 116044, China.|Department of Biochemistry, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Chengyi
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, 116044, China.|Department of Biochemistry, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Tao
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Ming-Zhong
authors.initials: MZ
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D050830:L-Amino Acid Oxidase / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D012910:Snake Venoms / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D012910:Snake Venoms; D016212:Transforming Growth Factor beta; D006861:Hydrogen Peroxide; D002374:Catalase; D050830:L-Amino Acid Oxidase