Cytotoxic activity of l-lysine alpha-oxidase against leukemia cells

Costa, Mariana; Silva, Roberto do Nascimento

doi:10.1016/j.semcancer.2021.09.015

Cited by 4 publications

(4 citation statements)

References 89 publications

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“…The activities of chitinases, cellulases, b-1,3-glucanases, b-1,6-glucanases, and xylanases were determined according to the technique for measuring the amount of reducing sugar [13], with some subsequent modifications. The reaction mixture consisted of 1.5 mL of 50 mM potassium phosphate buffer (pH 6.7) and substrate (0.5%)-chitin, laminarin, pustulan, or xylan.…”

Section: Enzyme Biosynthesis Evaluationmentioning

confidence: 99%

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Synthesis of Extracellular L-lysine-α-oxidase along with Degrading Enzymes by Trichoderma cf. aureoviride Rifai VKM F-4268D: Role in Biocontrol and Systemic Plant Resistance

Arinbasarova,

Botin,

Medentsev

et al. 2024

JoF

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When cultivating on wheat bran or deactivated fungal mycelium as a model of “natural growth”, the ability of Trichoderma to synthesize extracellular L-lysine-α-oxidase (LysO) simultaneously with cell-wall-degrading enzymes (proteases, xylanase, glucanases, chitinases, etc.), responsible for mycoparasitism, was shown. LysO, in turn, causes the formation of H2O2 and pipecolic acid. These compounds are known to be signaling molecules and play an important role in the induction and development of systemic acquired resistance in plants. Antagonistic effects of LysO have been demonstrated against phytopathogenic fungi and Gram-positive or Gram-negative bacteria with dose-dependent cell death. The antimicrobial effect of LysO decreased in the presence of catalase. The generating intracellular ROS in the presence of LysO was also shown in both bacteria and fungi, which led to a decrease in viable cells. These results suggest that the antimicrobial activity of LysO is due to two factors: the formation of exogenous hydrogen peroxide as a product of the enzymatic oxidative deamination of L-lysine and the direct interaction of LysO with the cell wall of the micro-organisms. Thus, LysO on its own enhances the potential of the producer in the environment; namely, the enzyme complements the strategy of the fungus in biocontrol and indirectly participates in inducing SAR and regulating the relationship between pathogens and plants.

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Section: Enzyme Biosynthesis Evaluationmentioning

confidence: 99%

“…Multiple in vitro and in vivo investigations have revealed the great potential of LysO for tumor enzyme therapy [12][13][14]. Therefore, LysO from Trichoderma cf.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Extracellular L-lysine-α-oxidase along with Degrading Enzymes by Trichoderma cf. aureoviride Rifai VKM F-4268D: Role in Biocontrol and Systemic Plant Resistance

Arinbasarova,

Botin,

Medentsev

et al. 2024

JoF

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“…It has been reported that some cancer cells lack the ability to synthesize some amino acids, so they depend on the exogenous supply of these nutrients to maintain their development and metabolism ( 68 ). To meet this metabolic demand, cancer cells increase the expression of transporters and enzymes involved in amino acid synthesis and metabolism ( 69 ), which may promote the deprivation of these nutrients in the TME and thus, the impairment of the effector functions of antitumor immune cells.…”

Section: Metabolic Reprogramming In the Tmementioning

confidence: 99%

Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment

et al. 2023

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The tumor microenvironment (TME) is a complex and constantly changing cellular system composed of heterogeneous populations of tumor cells and non-transformed stromal cells, such as stem cells, fibroblasts, endothelial cells, pericytes, adipocytes, and innate and adaptive immune cells. Tumor, stromal, and immune cells consume available nutrients to sustain their proliferation and effector functions and, as a result of their metabolism, produce a wide array of by-products that gradually alter the composition of the milieu. The resulting depletion of essential nutrients and enrichment of by-products work together with other features of the hostile TME to inhibit the antitumor functions of immune cells and skew their phenotype to promote tumor progression. This review briefly describes the participation of the innate and adaptive immune cells in recognizing and eliminating tumor cells and how the gradual metabolic changes in the TME alter their antitumor functions. In addition, we discuss the overexpression of the immune checkpoints and their ligands as a result of nutrient deprivation and by-products accumulation, as well as the amplification of the metabolic alterations induced by the immune checkpoints, which creates an immunosuppressive feedback loop in the TME. Finally, the combination of metabolic and immune checkpoint inhibitors as a potential strategy to treat cancer and enhance the outcome of patients is highlighted.

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“…Trichoderma harzianum is a filamentous fungus used as a biological agent against phytopathogens such as Botrytis , Rhizoctonia , and Fusarium which cause significant damage to several crops [ 19 ]. The mycoparasitic activity of some species of Trichoderma involves not only physical contact but also the synthesis of lytic enzymes such as l -lysine oxidase and other toxic components [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

The recombinant l-lysine α-oxidase from the fungus Trichoderma harzianum promotes apoptosis and necrosis of leukemia CD34 + hematopoietic cells

Costa,

Silva,

Guimarães

et al. 2024

Microb Cell Fact

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Background In hematologic cancers, including leukemia, cells depend on amino acids for rapid growth. Anti-metabolites that prevent their synthesis or promote their degradation are considered potential cancer treatment agents. Amino acid deprivation triggers proliferation inhibition, autophagy, and programmed cell death. l-lysine, an essential amino acid, is required for tumor growth and has been investigated for its potential as a target for cancer treatment. l-lysine α-oxidase, a flavoenzyme that degrades l-lysine, has been studied for its ability to induce apoptosis and prevent cancer cell proliferation. In this study, we describe the use of l-lysine α-oxidase (LO) from the filamentous fungus Trichoderma harzianum for cancer treatment. Results The study identified and characterized a novel LO from T. harzianum and demonstrated that the recombinant protein (rLO) has potent and selective cytotoxic effects on leukemic cells by triggering the apoptotic cascade through mitochondrial dysfunction. Conclusions The results support future translational studies using the recombinant LO as a potential drug for the treatment of leukemia.

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Cytotoxic activity of l-lysine alpha-oxidase against leukemia cells

Cited by 4 publications

References 89 publications

Synthesis of Extracellular L-lysine-α-oxidase along with Degrading Enzymes by Trichoderma cf. aureoviride Rifai VKM F-4268D: Role in Biocontrol and Systemic Plant Resistance

Synthesis of Extracellular L-lysine-α-oxidase along with Degrading Enzymes by Trichoderma cf. aureoviride Rifai VKM F-4268D: Role in Biocontrol and Systemic Plant Resistance

Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment

The recombinant l-lysine α-oxidase from the fungus Trichoderma harzianum promotes apoptosis and necrosis of leukemia CD34 + hematopoietic cells

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