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普通荨麻(Urtica dioica L.)植物凝集素对人急性髓系白血病细胞系凋亡相关基因表达的影响。

The Agglutinin of Common Nettle (Urtica dioica L.) Plant Effects on Gene Expression Related to Apoptosis of Human Acute Myeloid Leukemia Cell Line.

机构信息

School of Medicine, Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

出版信息

Biochem Genet. 2021 Aug;59(4):1049-1064. doi: 10.1007/s10528-020-10024-9. Epub 2021 Mar 6.

DOI:10.1007/s10528-020-10024-9
PMID:33675488
Abstract

Treatment of acute myeloid leukemia (AML) requires new drugs as result of a rise in new cases and high disease relapse. Plant lectins with the ability to bind carbohydrates on the cell surface have the potential to treat cancer. Urtica dioica L. agglutinin (UDA) is a low weight lectin with anti-benign prostatic hyperplasia (BPH) impact. Here, we examine the impact of UDA on HL-60 cell line. Cytotoxicity and cytostatic effects were assessed in HL-60 cells treated with UDA and vincristine (positive control). The effects of the lectin on cell cycle phases and cell death mechanism were surveyed by propidium iodide (PI) staining and annexin V/PI, respectively. The activation status of the apoptosis pathway was determined by western blotting. Finally, the expression levels of 84 genes were examined by the Human cancer drug target gene PCR array kit. The results indicated that the increase in UDA concentration inhibited the proliferation of HL-60 cells as well as apoptosis induction. Cell cycle analysis showed that the number of sub G1 cells increased essentially. Experimental observations showed that UDA can induce cell apoptosis through a caspase 9-dependent pathway. The expression changes of 21 genes confirmed the apoptotic events in HL-60 cells treated with UDA. In this, we have presented the first investigation on the cytotoxic and apoptotic effects of a lectin isolated from rhizomes and roots of Urtica dioica L. on human AML cells. Generally, the results suggest that UDA may have therapeutic value for leukemia and would be studied further as a new drug for AML later on.

摘要

急性髓细胞白血病(AML)的治疗需要新的药物,因为新病例的增加和疾病高复发率。具有结合细胞表面碳水化合物能力的植物凝集素有治疗癌症的潜力。荨麻凝集素(UDA)是一种低分子量的凝集素,具有抗良性前列腺增生(BPH)的作用。在这里,我们研究了 UDA 对 HL-60 细胞系的影响。用 UDA 和长春新碱(阳性对照)处理 HL-60 细胞,评估细胞毒性和细胞抑制作用。通过碘化丙啶(PI)染色和 Annexin V/PI 分别研究了凝集素对细胞周期各阶段和细胞死亡机制的影响。通过 Western blot 测定凋亡途径的激活状态。最后,通过人类癌症药物靶基因 PCR 阵列试剂盒检查 84 个基因的表达水平。结果表明,UDA 浓度的增加抑制了 HL-60 细胞的增殖以及诱导细胞凋亡。细胞周期分析表明,Sub G1 期细胞的数量显著增加。实验观察表明,UDA 可以通过 caspase 9 依赖的途径诱导细胞凋亡。UDA 处理的 HL-60 细胞中 21 个基因的表达变化证实了凋亡事件。在此,我们首次研究了从荨麻根茎和根中分离的凝集素对人 AML 细胞的细胞毒性和凋亡作用。总的来说,结果表明 UDA 可能对白血病具有治疗价值,并将进一步研究作为治疗 AML 的新药。

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