Withaferin A, a Cytotoxic Steroid from Vassobia breviflora, Induces Apoptosis in Human Head and Neck Squamous Cell Carcinoma
Withaferin A, a Cytotoxic Steroid from Vassobia breviflora, Induces Apoptosis in Human Head and Neck Squamous Cell Carcinoma
复制标题
DOI：
10.1021/np100112p
复制
发表时间：
2010-09-01
影响因子：
5.1
通讯作者：
Cohen, Mark S.
中科院分区：
文献类型：
--
作者：
Samadi, Abbas K.;Tong, Xiaoqin;Cohen, Mark S.
作为从植物生物多样性中发现药物线索的计划的一部分，本研究旨在探索来自选定的拉丁美洲植物的化合物的抗癌潜力。对短花Vassobia breviflora地上部分的粗提物进行生物测定指导分级分离，分离出了睡茄内酯型甾体内酯睡茄素A（1）。测试了该化合物对头颈部鳞状细胞癌（HNSCC）细胞系MDA 1986、JMAR、UM-SCC-2和JHU 011的抗增殖活性。通过MTS细胞毒性试验测定将细胞活力降低至50%的抑制浓度（IC 50），1降低细胞活力，IC 50值在0.5-2.2 μ M范围内。一项机制研究表明，1诱导HNSCC细胞凋亡和细胞死亡，以及细胞周期从G（0）/G（1）转变为G（2）/M。用1处理的细胞表现出Akt的失活和总Akt浓度的降低。本研究首次报道了醉茄素A（1）对头颈部鳞状细胞癌的抗增殖活性。
As part of a program to discover drug leads from plant biodiversity, the present investigation was undertaken to explore the anticancer potential of compounds derived from selected Latin American plants. Bioassay-guided fractionation of a crude extract of the aerial parts of Vassobia breviflora led to the isolation of the withanolide-type steroidal lactone withaferin A (1). This compound was tested for antiproliferative activity against the head and neck squamous cell carcinoma (HNSCC) cell lines, MDA1986, JMAR, UM-SCC-2, and JHU011. The inhibitory concentrations to reduce cell viability to 50% (IC50) were determined by the MTS cytotoxicity assay, and 1 reduced cell viability with IC50 values in the range 0.5-2.2 mu M. A mechanistic study showed that 1 induces apoptosis and cell death in HNSCC cells as well as a cell-cycle shift from G(0)/G(1) to G(2)/M. Cells treated with 1 exhibited inactivation of Akt and a reduction in total Akt concentration. This investigation constitutes the first report of the antiproliferative activity of withaferin A (1) against head and neck squamous carcinoma.