Hu Wan-Ping, Yu Hsin-Su, Chen Yan-Ren, Tsai Yi-Min, Chen Yin-Kai, Liao Chao-Cheng, Chang Long-Sen, Wang Jeh-Jeng
Faculty of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
Bioorg Med Chem. 2008 May 1;16(9):5295-302. doi: 10.1016/j.bmc.2008.03.003. Epub 2008 Mar 6.
A series of novel thiobenzanilides is described. These compounds have been previously found to show strong biological activity such as antimycotic and antifungal actions. This is the first demonstration on the mechanism of the anticancer effect of thiobenzanilide agents (4a-c) on human melanoma A375 cells. The cytotoxic studies of compounds 4a-c on human melanoma A375 cells indicate thiobenzanilides induced higher cytotoxicity than nitrobenzanilides (3a-c). In addition, DNA flow cytometric analysis shows that 4a-c displays a significant G2/M phase arrest, which progresses to early apoptosis as detected by flow cytometry after double-staining with annexin V and propidium iodide (PI). Because cellular apoptosis is often preceded by the disruption of mitochondrial function, the assessment of mitochondrial function in 4a-c-treated cells is worthy of investigation. Our data revealed that treatment of A375 cells with 4a-c resulted in the loss of mitochondrial membrane potential (DeltaPsi(mt)), a reduction of ATP synthesis, increased reactive oxygen species (ROS) generation, and activation of caspase-3. Thus, we suggest that 4a-c agents are potent inducers of cell apoptosis in A375 cells.
本文描述了一系列新型硫代苯甲酰苯胺。这些化合物此前已被发现具有强大的生物活性，如抗霉菌和抗真菌作用。这是首次关于硫代苯甲酰苯胺类药物（4a - c）对人黑色素瘤A375细胞抗癌作用机制的论证。化合物4a - c对人黑色素瘤A375细胞的细胞毒性研究表明，硫代苯甲酰苯胺比硝基苯甲酰苯胺（3a - c）诱导更高的细胞毒性。此外，DNA流式细胞术分析显示，4a - c导致显著的G2/M期阻滞，在用膜联蛋白V和碘化丙啶（PI）双重染色后通过流式细胞术检测发现其进一步发展为早期凋亡。由于细胞凋亡通常先于线粒体功能的破坏，因此评估4a - c处理细胞中的线粒体功能值得研究。我们的数据显示，用4a - c处理A375细胞会导致线粒体膜电位（ΔΨ(mt)）丧失、ATP合成减少、活性氧（ROS）生成增加以及半胱天冬酶 - 3激活。因此，我们认为4a - c类药物是A375细胞中细胞凋亡的有效诱导剂。
