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

Author:

Costa Mariana do Nascimento,Silva Thiago Aparecido,Guimarães Dimitrius Santiago Passos Simões Fr,Ricci-Azevedo Rafael,Teixeira Felipe Roberti,Silveira Leonardo Reis,Gomes Marcelo Damário,Faça Vítor Marcel,de Oliveira Eduardo Brandt,Calado Rodrigo T.,Silva Roberto N.

Abstract

Abstract 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.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Publisher

Springer Science and Business Media LLC

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