Isolation and characterization of ACTX-6: a cytotoxic L-amino acid oxidase from Agkistrodon acutus snake venom

Natural Product Research
Liang Zhang, W T Wu

Abstract

The characterization of an L-amino acid oxidase purified from Agkistrodon acutus snake venom was investigated. An L-amino acid oxidase (LAAO) was purified from A. acutus snake venom through DEAE Sepharose F.F. and Source 30 S chromatography. The molecular mass of this enzyme was determined by SDS-PAGE, size exclusion chromatography, and mass spectrometry. Substrate specificity, cytotoxicity, antitumor activity in vivo, and apoptosis-inducing activity were assayed. The LAAO purified from A. acutus snake venom was designated as ACTX-6. It is a covalently bound homodimer and its molecular mass is about 96 kDa. This enzyme preferred to oxidize hydrophobic L-amino acids; the best substrates were L-Met, L-Leu, L-Trp, and L-Phe. ACTX-6 demonstrated cytotoxicity in vitro and could inhibit tumor growth in vivo. Flow cytometry analysis showed that it could markedly increase accumulation of sub-G1 phase, which suggested that this enzyme could induce apoptosis. ACTX-6 could effectively inhibit tumor growth and it is a potential substance to develop into an antitumor drug.

References

Jul 17, 1995·Biochimica Et Biophysica Acta·M Zoratti, I Szabò
Jul 5, 1996·Biochemical and Biophysical Research Communications·S M Suhr, D S Kim
Dec 17, 1998·The Veterinary Record·C M AlmeidaW D da Silva
Sep 15, 1999·Toxicon : Official Journal of the International Society on Toxinology·Q Q HuangL W Niu
Feb 9, 2000·Journal of Bioenergetics and Biomembranes·E Fontaine, P Bernardi
Jul 6, 2000·Journal of the National Cancer Institute·P CostantiniG Kroemer
Apr 27, 2002·Annals of the New York Academy of Sciences·Vladimir P Skulachev
Aug 15, 2002·Toxicon : Official Journal of the International Society on Toxinology·Xiao-Yan Du, Kenneth J Clemetson
Mar 26, 2003·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Lian-Kun SunNobuya Morine
Sep 10, 2003·Biochemical and Biophysical Research Communications·Yu-Jie ZhangYun Zhang
Jan 17, 2004·Archives of Biochemistry and Biophysics·Nobuyuki KanzawaTakahide Tsuchiya
May 15, 2004·Bioorganic & Medicinal Chemistry·Rodrigo G StábeliAndreimar M Soares
Jun 30, 2004·Chemico-biological Interactions·Cristina MarzanoDolores Fregona
Jun 14, 2006·Apoptosis : an International Journal on Programmed Cell Death·Sudharsana Rao AndeElisa Ferrando-May

❮ Previous
Next ❯

Citations

Apr 1, 2014·BioMed Research International·Leonardo A CalderonAndreimar M Soares
Jun 19, 2014·The Journal of Venomous Animals and Toxins Including Tropical Diseases·Tássia R CostaSuely V Sampaio
Nov 20, 2014·BMC Complementary and Alternative Medicine·Durvanei Augusto MariaItamar Romano Garcia Ruiz
Jun 6, 2009·Cellular and Molecular Life Sciences : CMLS·R Doley, R M Kini
Jan 27, 2016·International Journal of Biological Macromolecules·Sandra Mara BurinFabíola Attié de Castro
Jul 10, 2010·Toxicon : Official Journal of the International Society on Toxinology·Poliana DeolindoElias W Alves
Mar 25, 2010·Toxicon : Official Journal of the International Society on Toxinology·Ya TangTianhan Kong
Feb 16, 2010·Toxicon : Official Journal of the International Society on Toxinology·V O AntonyukR S Stoika
Sep 23, 2008·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Raquel Melo AlvesSuely Vilela Sampaio
Apr 5, 2013·Basic & Clinical Pharmacology & Toxicology·Sandra M BurinFabíola A de Castro
Oct 15, 2013·Basic & Clinical Pharmacology & Toxicology·Mui Li LeeNget Hong Tan
May 15, 2012·Toxicon : Official Journal of the International Society on Toxinology·Chunmei GuoMing-Zhong Sun
Apr 9, 2020·Biochemical Society Transactions·Jia Jin Hiu, Michelle Khai Khun Yap
Nov 6, 2015·The Journal of Venomous Animals and Toxins Including Tropical Diseases·Cássio Prinholato da SilvaSuely V Sampaio
Jun 13, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Syafiq Asnawi Zainal AbidinRakesh Naidu
Feb 6, 2019·Toxins·Syafiq Asnawi Zainal AbidinRakesh Naidu
Jun 25, 2019·Toxicon : Official Journal of the International Society on Toxinology·Lougin M Abdel-GhaniMohamed A Abdel-Rahman

❮ Previous
Next ❯

Methods Mentioned

BETA
deamination
size exclusion chromatography
enzyme-linked immunosorbent assay
activated cell sorting
gel filtration
flow cytometry

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis