Camptothecin and khat (Catha edulis Forsk.) induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell lines.
Camptothecin and khat (Catha edulis Forsk.) induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell lines.
复制标题
DOI：
10.1186/1476-4598-8-101
复制
发表时间：
2009-11-13
期刊：
影响因子：
37.3
通讯作者：
Gjertsen BT
中科院分区：
文献类型：
--
作者：
Bredholt T;Dimba EA;Hagland HR;Wergeland L;Skavland J;Fossan KO;Tronstad KJ;Johannessen AC;Vintermyr OK;Gjertsen BT
一种有机提取物的休闲草药卡塔叶（catha edulis Forsk。）在体外引发各种白血病细胞系的细胞死亡。化学治疗剂喜树碱，一种植物生物碱拓扑异构酶I抑制剂，在一组急性髓性白血病细胞系中与阿拉伯茶并排进行测试，以阐明毒性机制。阿拉伯茶对MOLM-13细胞有深远的影响，诱导线粒体损伤，染色质边集和自噬的形态特征。阿拉伯茶对MOLM-13中线粒体超微结构的影响与强烈受损的常规呼吸相关，这种影响既没有在阿拉伯茶抗性MV-4 - 11细胞中发现，也没有在喜树碱处理的细胞中发现。抗凋亡Bcl-2蛋白的强制表达提供了对喜树碱诱导的细胞死亡的保护，部分对阿茶毒性。在MOLM-13细胞中，卡塔叶诱导的细胞死亡包括抗凋亡Mcl-1蛋白水平降低，而卡塔叶和喜树碱均诱导c-FLIPL裂解和半胱氨酸天冬氨酸蛋白酶原-8活化。与喜树碱相比，阿茶在敏感的白血病细胞中激活了一种独特的细胞死亡途径，涉及线粒体损伤和自噬的形态学特征。这表明，在寻找新的实验疗法时，应进一步探索阿拉伯茶。
An organic extract of the recreational herb khat (Catha edulis Forsk.) triggers cell death in various leukemia cell lines in vitro. The chemotherapeutics camptothecin, a plant alkaloid topoisomerase I inhibitor, was tested side-by-side with khat in a panel of acute myeloid leukemia cell lines to elucidate mechanisms of toxicity. Khat had a profound effect on MOLM-13 cells inducing mitochondrial damage, chromatin margination and morphological features of autophagy. The effects of khat on mitochondrial ultrastructure in MOLM-13 correlated with strongly impaired routine respiration, an effect neither found in the khat-resistant MV-4-11 cells nor in camptothecin treated cells. Enforced expression of anti-apoptotic Bcl-2 protein provided protection against camptothecin-induced cell death and partly against khat toxicity. Khat-induced cell death in MOLM-13 cells included reduced levels of anti-apoptotic Mcl-1 protein, while both khat and camptothecin induced c-FLIPL cleavage and procaspase-8 activation. Khat activated a distinct cell death pathway in sensitive leukemic cells as compared to camptothecin, involving mitochondrial damage and morphological features of autophagy. This suggests that khat should be further explored in the search for novel experimental therapeutics.
登录
查看更多内容
影响因子：
13.3
作者：
Maiuri, Maria Chiara;Criollo, Alfredo;Kroemer, Guido
通讯作者：
Kroemer, Guido
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Krueger, A;Schmitz, I;Kirchhoff, S
通讯作者：
Kirchhoff, S
影响因子：
20.3
作者：
Del Poeta, G;Venditti, A;Amadori, S
通讯作者：
Amadori, S
影响因子：
5.4
作者：
Al-Qirim, TM;Shahwan, M;Banu, N
通讯作者：
Banu, N