哈茨木霉重组 L-赖氨酸 α-氧化酶促进白血病 CD34+造血细胞的凋亡和坏死。
The recombinant L-lysine α-oxidase from the fungus Trichoderma harzianum promotes apoptosis and necrosis of leukemia CD34 + hematopoietic cells.
机构信息
Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Department of Cell Biology and Molecular and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
出版信息
Microb Cell Fact. 2024 Feb 14;23(1):51. doi: 10.1186/s12934-024-02315-2.
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.
背景
在血液系统癌症（包括白血病）中，细胞依赖氨基酸来快速生长。抑制其合成或促进其降解的抗代谢物被认为是有潜力的癌症治疗药物。氨基酸剥夺会触发增殖抑制、自噬和程序性细胞死亡。赖氨酸是一种必需氨基酸，是肿瘤生长所必需的，其作为癌症治疗靶点的潜力已被研究。降解赖氨酸的黄素酶赖氨酸α-氧化酶已被研究用于诱导细胞凋亡和预防癌细胞增殖。在这项研究中，我们描述了使用来自哈茨木霉的赖氨酸α-氧化酶（LO）进行癌症治疗。
结果
该研究鉴定并表征了来自哈茨木霉的一种新型 LO，并证明重组蛋白（rLO）通过线粒体功能障碍触发凋亡级联反应，对白血病细胞具有强大且选择性的细胞毒性作用。
结论
这些结果支持未来使用重组 LO 作为治疗白血病的潜在药物进行转化研究。
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