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

Anticancer enzyme L-lysine α-oxidase: Properties and application perspectives

Fungal L-lysine α-oxidase (1.4.3.14) (LO) from Trichoderma harzianum Rifai presents an oxidoreductase with a firmly attached coenzyme - FAD. This stable enzyme catalyzes an oxidative deamination of L-lysine yielding hydrogen peroxide, ammonia, and α-keto acid. LO exhibits antitumor activity toward 5 of 12 tested transplantable tumors. The sensitive tumors were ascitic hepatoma 22 (T/C = 201%, CR = 66%); mammary adenocarcinoma Ca-755 (TGI = 96%); melanoma B-16 (TGI = 81%); AKATOL (TGI = 75%); RSHM 5 (TGI = 79%). LO therapeutic activity was observed within a wide range of doses, 35-350 U/kg, by intraperitoneal daily injections for 5 d. Contrary to Escherichia coli L-asparaginase, LO demonstrates its antitumor activity by the low therapeutic doses in vivo within a wide range of optimal doses and through another antitumor spectrum. Fisher lymphadenosis L-5178y highly sensitive toward L-asparaginase appeared to be LO resistant. The possible mechanisms of LO antitumor activity through the key biochemical processes are discussed

Anticancer enzyme L-lysine alpha-oxidase - Properties and application perspectives

Fungal L-lysine a-oxidase (1.4.3.14) (LO) from Trichoderma harzianum Rifai presents an oxidoreductase with a firmly attached coenzyme--FAD. This stable enzyme catalyzes an oxidative deamination of L-lysine yielding hydrogen peroxide, ammonia, and a-keto acid. LO exhibits antitumor activity toward 5 of 12 tested transplantable tumors. The sensitive tumors were ascitic hepatoma 22 (T/C = 201%, CR = 66%); mammary adenocarcinoma Ca755 (TGI = 96%); melanoma B-16 (TGI = 81%); AKATOL (TGI = 75%); RSHM 5 (TGI = 79%). LO therapeutic activity was observed within a wide range of doses, 35-350 U/kg, by intraperitoneal daily injections for 5 d. Contrary to Escherichia coli L-asparaginase, LO demonstrates its antitumor activity by the low therapeutic doses in vivo within a wide range of optimal doses and through another antitumor spectrum. Fisher lymphadenosis L-5178y highly sensitive toward L-asparaginase appeared to be LO resistant. The possible mechanisms of LO antitumor activity through the key biochemical processes are discussed

Anticancer enzyme L-lysine α-oxidase: Properties and application perspectives

Fungal L-lysine α-oxidase (1.4.3.14) (LO) from Trichoderma harzianum Rifai presents an oxidoreductase with a firmly attached coenzyme - FAD. This stable enzyme catalyzes an oxidative deamination of L-lysine yielding hydrogen peroxide, ammonia, and α-keto acid. LO exhibits antitumor activity toward 5 of 12 tested transplantable tumors. The sensitive tumors were ascitic hepatoma 22 (T/C = 201%, CR = 66%); mammary adenocarcinoma Ca-755 (TGI = 96%); melanoma B-16 (TGI = 81%); AKATOL (TGI = 75%); RSHM 5 (TGI = 79%). LO therapeutic activity was observed within a wide range of doses, 35-350 U/kg, by intraperitoneal daily injections for 5 d. Contrary to Escherichia coli L-asparaginase, LO demonstrates its antitumor activity by the low therapeutic doses in vivo within a wide range of optimal doses and through another antitumor spectrum. Fisher lymphadenosis L-5178y highly sensitive toward L-asparaginase appeared to be LO resistant. The possible mechanisms of LO antitumor activity through the key biochemical processes are discussed

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

Anticancer enzyme L-lysine alpha-oxidase - Properties and application perspectives

Fungal L-lysine a-oxidase (1.4.3.14) (LO) from Trichoderma harzianum Rifai presents an oxidoreductase with a firmly attached coenzyme--FAD. This stable enzyme catalyzes an oxidative deamination of L-lysine yielding hydrogen peroxide, ammonia, and a-keto acid. LO exhibits antitumor activity toward 5 of 12 tested transplantable tumors. The sensitive tumors were ascitic hepatoma 22 (T/C = 201%, CR = 66%); mammary adenocarcinoma Ca755 (TGI = 96%); melanoma B-16 (TGI = 81%); AKATOL (TGI = 75%); RSHM 5 (TGI = 79%). LO therapeutic activity was observed within a wide range of doses, 35-350 U/kg, by intraperitoneal daily injections for 5 d. Contrary to Escherichia coli L-asparaginase, LO demonstrates its antitumor activity by the low therapeutic doses in vivo within a wide range of optimal doses and through another antitumor spectrum. Fisher lymphadenosis L-5178y highly sensitive toward L-asparaginase appeared to be LO resistant. The possible mechanisms of LO antitumor activity through the key biochemical processes are discussed

Biological properties of L-lysine α-oxidase in native and conjugated form

The significant difference between biological properties of L-lysine-α-oxidase from Trichoderma harzianum Rifai (LO) and L-asparaginase from E.coli has been observed in vitro and in vivo. High antitumor activity was shown against 8 types of murine and rat transplanted tumors with a wide range of LO therapeutic doses: 35-350 U/mg. The LO conjugates with monoclonal antibodies CD5 specific to the surface of cell line Yurkat were obtained without significant loss of either enzymatic and cytotoxic activity or immunological specificity. The further perspective investigation for the clinical application of the native or conjugated enzymes is discussed

Biological properties of L-lysine α-oxidase in native and conjugated form

The significant difference between biological properties of L-lysine-α-oxidase from Trichoderma harzianum Rifai (LO) and L-asparaginase from E.coli has been observed in vitro and in vivo. High antitumor activity was shown against 8 types of murine and rat transplanted tumors with a wide range of LO therapeutic doses: 35-350 U/mg. The LO conjugates with monoclonal antibodies CD5 specific to the surface of cell line Yurkat were obtained without significant loss of either enzymatic and cytotoxic activity or immunological specificity. The further perspective investigation for the clinical application of the native or conjugated enzymes is discussed