研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

大戟叶大戟 (Ferula flabelliloba) 中的香豆素,即聚香豆素,对成人 T 细胞白血病/淋巴瘤细胞产生了毒性影响。

Conferone, a coumarin from Ferula flabelliloba, induced toxic effects on adult T-cell leukemia/lymphoma cells.

发表日期:2023
作者: Houshang Rafatpanah, Marziyeh Golizadeh, Maryam Mahdifar, Shakiba Mahdavi, Mehrdad Iranshahi, Fatemeh B Rassouli
来源: Cellular & Molecular Immunology

摘要:

成人T细胞白血病/淋巴瘤(ATL)是由HTLV-1感染引起的一种淋巴肿瘤,具有明显的地理分布。尽管在癌症治疗方面取得了进展,ATL的平均生存率仍然很低。Conferone是从阿魏属植物中提取的一种天然香豆素,具有广泛的药理效应。为了寻找一种新的化疗药物,我们研究了Conferone对ATL细胞的细胞毒作用。为了获得Conferone,我们将黄柏根的甲醇提取物经过硅胶柱层析,并通过1H-和13C-NMR来确认其结构。对于细胞毒性测定,我们将MT-2细胞分别用不同浓度(2.5、5、10、20和40 µM)的Conferone处理24、48和72小时,并通过使用alamarBlue 进行比色测定来评估细胞的存活率。细胞周期通过PI染色和流式细胞术进行分析,而qPCR则用于研究候选基因的表达。得到的结果表明,Conferone以时间和剂量依赖的方式显著诱导MT-2细胞的细胞毒作用。此外,在Conferone处理后发现细胞在细胞周期的亚G1期中累积。此外,Conferone还降低了MT-2细胞中CDK6、c-MYC、CFLIPL和NF-κB(Rel-A)的表达。因此,虽然还需要进行辅助研究来更准确地定义其作用机制,但Conferone可能被认为是一种对抗ATL的强效药物。
Adult T-cell leukemia/lymphoma (ATL) is a lymphoid malignancy caused by HTLV-1 infection, with distinct geographical distribution. Despite advances in cancer treatment, the average survival rate of ATL is low. Conferone is a natural coumarin extracted from Ferula species with a wide range of pharmaceutical effects. In search for a novel chemotherapeutic agent, we investigated the cytotoxicity of conferone on ATL cells.To obtain conferone, the methanolic extract of the roots of F. flabelliloba was subjected to silica gel column chromatography, followed by 1H- and 13C-NMR to confirm its structure. For cytotoxicity assay, MT-2 cells were treated with different concentrations of conferone (2.5, 5, 10, 20, and 40 µM) for 24, 48, and 72 h, and viability was evaluated by a colorimetric assay using alamarBlue. Cell cycle was analyzed by PI staining and flow cytometry, and qPCR was used to study the expression of candidate genes.Obtained findings indicated that conferone induced considerable cytotoxic effects on MT-2 cells in a time- and dose-dependent manner. In addition, accumulation of cells in the sub-G1 phase of the cell cycle was detected upon conferone administration. Moreover, conferone reduced the expression of CDK6, c-MYC, CFLIPL, and NF-κB (Rel-A) in MT-2 cells. Accordingly, conferone could be considered as a potent agent against ATL, although complementary investigations are required to define more precisely its mechanism of action.