Department of Oral Pathology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeon-ju, Republic of Korea.
Eur J Cancer Prev. 2010 Mar;19(2):153-9. doi: 10.1097/CEJ.0b013e328333d088.
Cruciferous vegetables contain isothiocyanates including diindolylmethane (DIM) that exhibit cancer chemopreventive effects. We developed a series of synthetic ring-substituted DIM analogs including 5,5'-dibromoDIM that exhibited better inhibitory activity in breast and colon cancer cells than DIM. In this study, we investigated whether 5,5'-dibromoDIM inhibits the proliferation of KB and YD-10B oral squamous carcinoma cell lines. 5,5'-dibromoDIM decreased the cell survival and inhibited the growth of oral cancer cells. Exposure of KB and YD-10B cells to 5,5'-dibromoDIM induced caspase-dependent apoptosis evidenced by poly-ADP ribose polymerase cleavage, accumulation of sub-G1 population, and nuclear condensation and fragmentation. In addition, apoptotic cell death was correlated with damage to the mitochondrial membrane potential through a decrease in the level of Bcl-2 protein expression. Mechanistic studies showed that mitochondria-dependent apoptosis induced by 5,5'-dibromoDIM was mediated by the p38 mitogen-activated protein kinase pathway but not the ERK1/2 and JNK pathway. These results highlight 5,5'-dibromoDIM as an important chemopreventive agent for the clinical treatment of oral cancer through the p38 mitogen-activated protein kinase pathway.
十字花科蔬菜含有异硫氰酸酯，包括二吲哚甲烷（DIM），具有抗癌化学预防作用。我们开发了一系列合成的环取代 DIM 类似物，包括 5,5'-二溴 DIM，它在乳腺癌和结肠癌细胞中的抑制活性比 DIM 更好。在这项研究中，我们研究了 5,5'-二溴 DIM 是否抑制 KB 和 YD-10B 口腔鳞状癌细胞系的增殖。5,5'-二溴 DIM 降低了细胞存活率并抑制了口腔癌细胞的生长。暴露于 5,5'-二溴 DIM 的 KB 和 YD-10B 细胞诱导 caspase 依赖性细胞凋亡，证据是聚 ADP 核糖聚合酶切割、亚 G1 群体积累以及核浓缩和碎裂。此外，通过降低 Bcl-2 蛋白表达水平，凋亡细胞死亡与线粒体膜电位损伤相关。机制研究表明，5,5'-二溴 DIM 诱导的线粒体依赖性细胞凋亡是由 p38 丝裂原活化蛋白激酶途径介导的，而不是 ERK1/2 和 JNK 途径。这些结果强调了 5,5'-二溴 DIM 通过 p38 丝裂原活化蛋白激酶途径作为口腔癌临床治疗的重要化学预防剂。
