Department of Surgery, School of Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
J Nat Prod. 2010 Sep 24;73(9):1476-81. doi: 10.1021/np100112p.
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% (IC(50)) were determined by the MTS cytotoxicity assay, and 1 reduced cell viability with IC(50) values in the range 0.5-2.2 μM. 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.
作为从植物生物多样性中发现药物先导物计划的一部分，本研究旨在探索源自拉丁美洲选定植物的化合物的抗癌潜力。对 Vassobia breviflora 地上部分的粗提取物进行生物活性导向分离，得到了具有螺内酯型甾体内酯结构的 withaferin A（1）。对该化合物进行了对头颈鳞状细胞癌（HNSCC）细胞系 MDA1986、JMAR、UM-SCC-2 和 JHU011 的抗增殖活性测试。通过 MTS 细胞毒性测定法确定抑制细胞活力至 50%的浓度（IC50），1 的 IC50 值范围为 0.5-2.2 μM。机制研究表明，1 可诱导 HNSCC 细胞凋亡和死亡，并使细胞周期从 G0/G1 期向 G2/M 期转变。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 withaferin A（1）对头颈鳞状癌的增殖抑制活性。
