title: Enzymatic properties and anticancer activity of L-lysine α-oxidase from Trichoderma cf. aureoviride Rifai BKMF-4268D.
abstract: L-Lysine α-oxidase (LO) from a novel Trichoderma strain: Trichoderma cf. aureoviride Rifai shows favorable biochemical and kinetic properties (Km for L-lysine of 17.9 µmol/l, optimum pH 8.0, high stability) and significant antiproliferative activity both in vitro and in vivo. The molecular weight of LO was determined to be 115-116 kDa; the active dimer consists of two identical 57-58 kDa subunits. LO shows considerable cytotoxicity against the following tumor cell lines: K562, LS174T, HT29, SCOV3, PC3, and MCF7, with the inhibition concentration (IC50) ranging from 3.0×10 to 7.8×10 U/ml (3.2×10 to 8.2×10 mg/ml). Two human colon cancer xenografts HCT116 and LS174T and breast adenocarcinoma T47D implanted subcutaneously into Balb/c nude mice showed high sensitivity to LO with a T/C of 12, 37, and 36%, respectively (P<0.05). The antitumor efficacy of LO was observed in the absence of pronounced morbidity or toxicity in vivo. Taken together, these data suggest that LO may be considered as an effective anticancer agent for the treatment of solid tumors in vivo. This study presents promising data on the possible application of LO in clinical oncology for patients with colorectal cancer.
authors.affiliation: Federal State Budgetary Institution, N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia. vadimpokrovsky@gmail.com
authors.forename: Vadim S
authors.initials: VS
authors.lastname: Pokrovsky
authors.forename: Helen M
authors.initials: HM
authors.lastname: Treshalina
authors.forename: Elena V
authors.initials: EV
authors.lastname: Lukasheva
authors.forename: Ludmila A
authors.initials: LA
authors.lastname: Sedakova
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Medentzev
authors.forename: Anna Yu
authors.initials: AY
authors.lastname: Arinbasarova
authors.forename: Temirbolat T
authors.initials: TT
authors.lastname: Berezov
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004795:Enzyme Stability; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism* / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008970:Molecular Weight; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D055503:Protein Multimerization; D013379:Substrate Specificity; D013997:Time Factors; D014242:Trichoderma / Q000201:enzymology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005656:Fungal Proteins; D000594:Amino Acid Oxidoreductases; C041123:L-lysine oxidase; D008239:Lysine