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基于 DNA 碎片因子 40 的癌症治疗方法:一篇综述文章。

DNA fragmentation factor 40-based therapeutic approaches for cancer: a review article.

机构信息

Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Hezar Jarib Ave., Isfahan, Iran.

Bioinformatics Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Med Oncol. 2024 Oct 14;41(11):264. doi: 10.1007/s12032-024-02511-5.

DOI:10.1007/s12032-024-02511-5
PMID:39397131
Abstract

DNA Fragmentation Factor (DFF) is a heterodimer protein involved in DNA fragmentation during apoptosis, which acts as a trigger downstream of caspase-3 activation. DFF40 catalytically active homo-oligomers break down chromosomal DNA. Previous scientific investigations have revealed a link between DFF40 expression changes and various cancers. DFF40 deletion or down-regulation has been observed in some cancers. Consequently, therapeutic strategies involving the DFF40 molecule compensating led to an increased rate of cancer cell apoptosis. In this review article, we aimed to introduce cancers with low expression of this protein first. The second part of this paper focuses on studies that utilized exogenous DFF40 protein produced by recombinant DNA technology and surveyed during in vitro and in vivo tests. Finally, compensation for diminished expression of the mentioned protein via gene therapy-based techniques to make up for this apoptotic molecule's low expression is the topic of the last part of this review article.

摘要

DNA 断裂因子(DFF)是一种参与细胞凋亡过程中 DNA 片段化的异源二聚体蛋白,作为 caspase-3 激活下游的触发因子。DFF40 催化活性同型寡聚体分解染色体 DNA。先前的科学研究表明,DFF40 表达变化与各种癌症之间存在关联。在一些癌症中观察到 DFF40 的缺失或下调。因此,涉及 DFF40 分子补偿的治疗策略导致癌细胞凋亡率增加。在这篇综述文章中,我们首先旨在介绍这种蛋白低表达的癌症。本文的第二部分重点介绍了利用重组 DNA 技术产生的外源性 DFF40 蛋白并在体外和体内试验中进行调查的研究。最后,通过基于基因治疗的技术来补偿所述蛋白表达的降低,以弥补这种凋亡分子的低表达,是本文最后一部分的主题。

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DNA fragmentation factor 40-based therapeutic approaches for cancer: a review article.基于 DNA 碎片因子 40 的癌症治疗方法:一篇综述文章。
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Modulation of DNA fragmentation factor 40 nuclease activity by poly(ADP-ribose) polymerase-1.聚(ADP - 核糖)聚合酶 -1对DNA片段化因子40核酸酶活性的调节作用
J Biol Chem. 2005 Apr 15;280(15):15141-7. doi: 10.1074/jbc.M413147200. Epub 2005 Feb 9.
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Non-endometrioid and high-grade endometrioid endometrial cancers show DNA fragmentation factor 40 (DFF40) and B-cell lymphoma 2 protein (BCL2) underexpression, which predicts disease-free and overall survival, but not DNA fragmentation factor 45 (DFF45) underexpression.非子宫内膜样和高级别子宫内膜样癌表现出 DNA 碎片因子 40(DFF40)和 B 细胞淋巴瘤 2 蛋白(BCL2)表达不足,这预测了无病生存和总生存,但不能预测 DNA 碎片因子 45(DFF45)表达不足。
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Caspase-activated DNase/DNA fragmentation factor 40 mediates apoptotic DNA fragmentation in transient cerebral ischemia and in neuronal cultures.半胱天冬酶激活的脱氧核糖核酸酶/DNA片段化因子40在短暂性脑缺血和神经元培养中介导凋亡性DNA片段化。
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Apoptotic DNA degradation into oligonucleosomal fragments, but not apoptotic nuclear morphology, relies on a cytosolic pool of DFF40/CAD endonuclease.细胞凋亡时 DNA 降解为寡核苷酸片段,但不依赖于凋亡核形态,这依赖于细胞质中 DFF40/CAD 内切核酸酶的池。
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本文引用的文献

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Production of recombinant DNA fragmentation factor 40 in fusion to an antimicrobial peptide from spider venom and evaluation of its cytotoxic effects.与蜘蛛毒液抗菌肽融合的重组DNA片段化因子40的生产及其细胞毒性作用评估。
Res Pharm Sci. 2024 Feb 6;19(1):93-104. doi: 10.4103/1735-5362.394824. eCollection 2024 Feb.
2
Review of cancer cell resistance mechanisms to apoptosis and actual targeted therapies.癌细胞对凋亡的抗性机制及当前靶向治疗的综述。
J Cell Biochem. 2022 Nov;123(11):1736-1761. doi: 10.1002/jcb.30173. Epub 2021 Nov 17.
3
Fusion of apoptosis-related protein Cytochrome c with anti-HER-2 single-chain antibody targets the suppression of HER-2+ breast cancer.
细胞色素 c 与抗 HER-2 单链抗体融合靶向抑制 HER-2+乳腺癌的细胞凋亡。
J Cell Mol Med. 2021 Nov;25(22):10638-10649. doi: 10.1111/jcmm.17001. Epub 2021 Oct 25.
4
DFF40 deficiency in cancerous T cells is implicated in chemotherapy drug sensitivity and resistance through the regulation of the apoptotic pathway.DFF40 缺乏可通过调节凋亡途径影响癌细胞对化疗药物的敏感性和耐药性。
Biochem Pharmacol. 2021 Dec;194:114801. doi: 10.1016/j.bcp.2021.114801. Epub 2021 Oct 20.
5
Survivin Promoter-Driven DFF40 Gene Expression Sensitizes Melanoma Cancer Cells to Chemotherapy.Survivin 启动子驱动 DFF40 基因表达使黑色素瘤癌细胞对化疗敏感。
Int J Toxicol. 2021 Jul-Aug;40(4):380-387. doi: 10.1177/10915818211014170. Epub 2021 May 7.
6
Design and characterization of a recombinant immunotoxin for targeted therapy of breast cancer cells: In vitro and in silico analyses.设计和鉴定一种针对乳腺癌细胞的靶向治疗用重组免疫毒素:体外和计算机模拟分析。
Life Sci. 2021 Jan 15;265:118866. doi: 10.1016/j.lfs.2020.118866. Epub 2020 Dec 7.
7
Mitochondria as multifaceted regulators of cell death.线粒体作为细胞死亡的多面调节者。
Nat Rev Mol Cell Biol. 2020 Feb;21(2):85-100. doi: 10.1038/s41580-019-0173-8. Epub 2019 Oct 21.
8
Antifungal activity of spider venom-derived peptide lycosin-I against Candida tropicalis.蜘蛛毒液衍生肽 lycosin-I 对热带念珠菌的抗真菌活性。
Microbiol Res. 2018 Nov;216:120-128. doi: 10.1016/j.micres.2018.08.012. Epub 2018 Aug 27.
9
An intrinsic DFF40/CAD endonuclease deficiency impairs oligonucleosomal DNA hydrolysis during caspase-dependent cell death: a common trait in human glioblastoma cells.内源性DFF40/CAD核酸内切酶缺陷会损害半胱天冬酶依赖性细胞死亡过程中的寡核小体DNA水解:人胶质母细胞瘤细胞的共同特征。
Neuro Oncol. 2016 Jul;18(7):950-61. doi: 10.1093/neuonc/nov315. Epub 2016 Jan 10.
10
Sensitization of breast cancer cells to doxorubicin via stable cell line generation and overexpression of DFF40.通过稳定细胞系的建立和DFF40的过表达使乳腺癌细胞对阿霉素敏感化。
Biochem Cell Biol. 2015 Dec;93(6):604-10. doi: 10.1139/bcb-2015-0007. Epub 2015 Sep 15.