Enzymatic properties and anticancer activity of L-lysine α-oxidase from Trichoderma cf. aureoviride Rifai BKMF-4268D

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 3.0×10-6 to 7.8×10 -2 U/ml (3.2×10-8 to 8.2×10-4 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. © 2013 Wolters Kluwer Health | Lippincott Williams &Wilkins.

Authors
Pokrovsky V.S.1 , Treshalina H.M.1 , Lukasheva E.V. 2 , Sedakova L.A.1 , Medentzev A.G.3 , Arinbasarova A.Y.3 , Berezov T.T. 2
Number of issue
8
Language
English
Pages
846-851
Status
Published
Volume
24
Year
2013
Organizations
  • 1 Federal State Budgetary Institution, N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoye Shosse 24, 115478 Moscow, Russian Federation
  • 2 Department of Biochemistry, Russian Peoples' Friendship University Moscow, Pushchino, Russian Federation
  • 3 G.K. Scryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Pushchino, Russian Federation
Keywords
anticancer activity; L-lysine a-oxidase; Trichoderma cf. aureoviride Rifai
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