Abstract：
UNASSIGNED: Following the success of natural compounds for treating solid tumors, interest in applying such agents for treating hematologic malignancies has been fired up more strikingly. Thus far, anti-leukemic effects of several compounds have been examined in different leukemia cell lines, especially in acute lymphoblastic leukemia. The agent that has recently attracted tremendous attention is Britannin, which is derived from Inula aucheriana DC., a plant that grows in Iran (Azerbaijan) and Türkiye. In this study, we evaluated the effects of this compound in myeloid leukemia for the first time.
UNASSIGNED: We treated chronic myeloid leukemia (CML)-derived K562 and acute myeloid leukemia (AML)-derived U937 cells with different concentrations of britannin. We used several assays, including trypan blue, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, bromodeoxyuridine/5-bromo-2\'-deoxyuridine, flow cytometry, and quantitative real-time polymerase chain reaction analysis, to study anti-leukemic effects of the compound.
UNASSIGNED: Our results show that while britannin remarkably reduced the survival of both cell lines in a concentrations-dependent manner, it had cytotoxic effects neither on mouse fibroblast-derived L929 cells nor on normal peripheral mononuclear cells. Moreover, among the tested cell lines, the viability of CML-derived K562 cells was inhibited at higher concentrations of the compound compared with AML-derived U937 cells. We found that britannin induced apoptotic cell death in both cell lines by altering the expression of anti- and pro-apoptotic genes. Britannin also hampered proliferative capacity of the cells in a p21/p27-dependent manner.
UNASSIGNED: Overall, we suggest that based on the lack of toxicity on the normal cells and valuable anti-leukemic activities, britannin could be a promising agent in the treatment strategies of both CML and AML. However, further investigations must more precisely study this compound\'s mechanism of action and evaluate its safety profile.
UNASSIGNED: We treated chronic myeloid leukemia (CML)-derived K562 and acute myeloid leukemia (AML)-derived U937 cells with different concentrations of britannin. We used several assays, including trypan blue, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, bromodeoxyuridine/5-bromo-2\'-deoxyuridine, flow cytometry, and quantitative real-time polymerase chain reaction analysis, to study anti-leukemic effects of the compound.
UNASSIGNED: Our results show that while britannin remarkably reduced the survival of both cell lines in a concentrations-dependent manner, it had cytotoxic effects neither on mouse fibroblast-derived L929 cells nor on normal peripheral mononuclear cells. Moreover, among the tested cell lines, the viability of CML-derived K562 cells was inhibited at higher concentrations of the compound compared with AML-derived U937 cells. We found that britannin induced apoptotic cell death in both cell lines by altering the expression of anti- and pro-apoptotic genes. Britannin also hampered proliferative capacity of the cells in a p21/p27-dependent manner.
UNASSIGNED: Overall, we suggest that based on the lack of toxicity on the normal cells and valuable anti-leukemic activities, britannin could be a promising agent in the treatment strategies of both CML and AML. However, further investigations must more precisely study this compound\'s mechanism of action and evaluate its safety profile.
摘要：
■随着天然化合物治疗实体肿瘤的成功，对应用这些药物治疗血液系统恶性肿瘤的兴趣更加引人注目。到目前为止,已经在不同的白血病细胞系中检查了几种化合物的抗白血病作用，尤其是急性淋巴细胞白血病。最近引起极大关注的特工是不列颠宁，源自InulaaucherianaDC。,一种生长在伊朗（阿塞拜疆）和蒂尔基耶的植物。在这项研究中,我们首次评估了该化合物对髓系白血病的疗效.
■我们用不同浓度的Britannin治疗慢性髓性白血病（CML）衍生的K562和急性髓性白血病（AML）衍生的U937细胞。我们使用了几种检测方法,包括锥虫蓝,3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物，溴脱氧尿苷/5-溴-2'-脱氧尿苷，流式细胞术,和定量实时聚合酶链反应分析，研究该化合物的抗白血病作用。
■我们的结果表明，虽然Britannin以浓度依赖的方式显着降低了两种细胞系的存活率，它对小鼠成纤维细胞来源的L929细胞和正常外周单核细胞均无细胞毒性作用.此外，在测试的细胞系中，与AML来源的U937细胞相比,在更高浓度的化合物下,CML来源的K562细胞的活力受到抑制。我们发现Britannin通过改变抗凋亡基因和促凋亡基因的表达来诱导两种细胞系中的凋亡细胞死亡。Britannin还以p21/p27依赖性方式阻碍了细胞的增殖能力。
■总的来说，我们建议基于对正常细胞缺乏毒性和有价值的抗白血病活性，Britannin在CML和AML的治疗策略中可能是一种有前途的药物.然而,进一步的研究必须更精确地研究该化合物的作用机制，并评估其安全性。
■我们用不同浓度的Britannin治疗慢性髓性白血病（CML）衍生的K562和急性髓性白血病（AML）衍生的U937细胞。我们使用了几种检测方法,包括锥虫蓝,3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物，溴脱氧尿苷/5-溴-2'-脱氧尿苷，流式细胞术,和定量实时聚合酶链反应分析，研究该化合物的抗白血病作用。
■我们的结果表明，虽然Britannin以浓度依赖的方式显着降低了两种细胞系的存活率，它对小鼠成纤维细胞来源的L929细胞和正常外周单核细胞均无细胞毒性作用.此外，在测试的细胞系中，与AML来源的U937细胞相比,在更高浓度的化合物下,CML来源的K562细胞的活力受到抑制。我们发现Britannin通过改变抗凋亡基因和促凋亡基因的表达来诱导两种细胞系中的凋亡细胞死亡。Britannin还以p21/p27依赖性方式阻碍了细胞的增殖能力。
■总的来说，我们建议基于对正常细胞缺乏毒性和有价值的抗白血病活性，Britannin在CML和AML的治疗策略中可能是一种有前途的药物.然而,进一步的研究必须更精确地研究该化合物的作用机制，并评估其安全性。
