欢迎访问《中山大学学报(自然科学版)(中英文)》! English Version 维普资讯 中国知网 万方数据
研究论文 | 更新时间:2023-12-11
    • 原小檗碱衍生物诱导急性淋巴白血病细胞凋亡活性及PAMPA研究

    • Antineoplastic effects and PAMPA studies of protoberberine derivatives: induce apoptosis activities in acute lymphoid leukemia cells

    • 周杰彬

      ,  

      邓春梅

      ,  

      施晓柯

      ,  

      项琪

      ,  

      吴启丽

      ,  

      潘景轩

      ,  

      庞冀燕

      ,  
    • 中山大学学报(自然科学版)(中英文)   2016年55卷第5期 页码:66-72
    • 纸质出版日期:2016

      网络出版日期:2016-10-25

    扫 描 看 全 文

  • 引用本文

    阅读全文PDF

  • 周杰彬, 邓春梅, 施晓柯, 等. 原小檗碱衍生物诱导急性淋巴白血病细胞凋亡活性及PAMPA研究[J]. 中山大学学报(自然科学版)(中英文), 2016,55(5):66-72. DOI:

    ZHOU Jiebin, DENG Chunmei, SHI Xiaoke, et al. Antineoplastic effects and PAMPA studies of protoberberine derivatives: induce apoptosis activities in acute lymphoid leukemia cells[J]. Acta Scientiarum Naturalium Universitatis SunYatseni, 2016,55(5):66-72. DOI:

  •  
  •  
    论文导航

    摘要

    测定了15个原小檗碱衍生物(3-17)及小檗碱(1)和药根碱(2)抑制急性淋巴白血病细胞(包括Reh 和 Nalm-6 细胞)增殖的活性。其中化合物4(9-溴乙基小檗碱),5(9-氯乙基小檗碱)和6(9-溴丙基小檗碱)表现出最为突出的抑制活性:在Reh细胞中,IC50值分别为0.45、0.39和0.57 μmol/L;在Nalm-6细胞中,IC50值分别为3.6, 4.3和1.17 μmol/L。活性均强于先导化合物小檗碱和药根碱(后两者的IC50值均大于20 μmol/L)。此外,化合物4和5能够剂量依赖的通过裂解PARP诱导急性淋巴白血病细胞凋亡,降低procaspase-3的浓度,增加活性caspase-3水平,同时提高细胞质中的细胞色素C水平。进一步,Reh细胞用0.5 μmol/L的4和5处理36 h,能够显著下调β-catenin蛋白的表达,以上实验结果证明了这类化合物抑制肿瘤细胞增殖的作用机制可能与Wnt/β-catenin 通路相关。化合物1、4、5、7和11的PAMPA膜渗透实验说明,C-9位取代的小檗碱衍生物可以提高化合物的细胞膜渗透性。

    Abstract

    In the present study, 15 derivatives of protoberberine (3-17) along with berberine (1) and jatrorrhizine (2) were evaluated for their antineoplastic activities against acute lymphoid leukemia cells (including Reh and Nalm-6 cells) in terms of proliferation inhibition. Compounds 4 (9-bromoethylberberine), 5 (9-chloroethylberberine) and 6 (9-bromopropylberberine) showed most significant inhibitory activities with IC50values of 0.45, 0.39, and 0.57 μmol/L against Reh cells, while Nalm-6 cells were less sensitive to 4,5,6, with IC50values of 3.6, 4.3 and 1.17 μmol/L, respectively, which were both stronger than that of the lead compound berberine (1)  and jatrorrhizine (2) (> 20 μmol/L, respectively). Furthermore, 4 and 5 could induce apoptosis in acute lymphoid leukemia cells as evidenced by cleavage of PARP in a dosedependent manner, decrease of procaspase-3, increase of active caspase-3 and increase of the levels of cytochrome c in cytoplasm. Moreover, the Reh cells treated with 4 and 5 at the concentration of 0.5 μmol/L for 36 h could significantly lead to the down regulation of β-catenin, and the result demonstrated that the mechanism of the derivatives on tumor were partially involved in the Wnt/β-catenin signal pathway. A PAMPA permeability study of 1, 4, 5, 7 and 11 suggested that side chain substituted derivatives in 9-position could improve the membrane permeability of berberine. It will be helpful for application in vivo assay. These findings suggest that these derivertives may be considered for future studies as promising therapeutic candidate for acute lymphoid leukemia.

    关键词

    原小檗碱; 衍生物; 抗肿瘤活性; PAMPA; 细胞凋亡

    Keywords

    protoberberine; derivatives; antineoplastic activities; PAMPA; apoptosis

    0

    浏览量

    203

    下载量

    0

    CSCD

    文章被引用时,请邮件提醒。
    提交
    工具集
    下载
    参考文献导出
    分享
    收藏
    添加至我的专辑

    相关文章

    α-倒捻子素衍生物合成及其抑制磷酸二酯酶4活性研究
    两种昆虫杆状病毒诱导的细胞凋亡
    OA对人肝细胞HL-7702和肝癌细胞Bel-7402增殖的影响和对细胞凋亡的诱导作用研究
    癌症相关促凋亡蛋白Par-4的信号转导途径预测研究
    Notch1信号通路在雷公藤甲素所致肝细胞毒性的作用及机制

    相关作者

    何细新
    黄仪有
    罗海彬
    刘昊柏
    于思
    朱嘉琪
    梁津豪
    黄悦

    相关机构

    广州中医药大学中药学院
    中山大学药学院
    中山大学生物防治国家重点实验室
    中国科学院海洋研究所海洋生态与环境科学重点实验室
    0