Department of Medical Technology, Fooyin University, Ta-Liao, Kaohsiung, Taiwan.
J Agric Food Chem. 2010 May 12;58(9):5604-11. doi: 10.1021/jf904260b.
The anticancer effects of 6-dehydrogingerdione (6-DG), a compound isolated from the rhizomes of Zingiber officinale , and its mechanisms of sensitization to TRAIL-induced apoptosis were studied using human hepatoblastoma Hep G2 cells. This study demonstrates for the first time that 6-DG-induced apoptosis might be executed via mitochondrial- and Fas receptor-mediated pathways. Further studies also demonstrated that 6-DG could sensitize Hep G2 cells to TRAIL-induced apoptosis. 6-DG also up-regulated Ser-15 phosphorylation and evoked p53 nuclear translocation. Abrogation of p53 expression by p53 small interfering RNA significantly attenuated 6-DG-induced DR5 expression, thus rendering these cells resistant to TRAIL-induced apoptosis. DR5 expression after 6-DG treatment was accompanied by provoking intracellular reactive oxygen species (ROS) generation. Pretreatment with N-acetyl-l-cysteine (NAC) attenuated 6-DG-induced DR5 expression and inhibited TRAIL-induced apoptosis. In contrast to Hep G2 cells, DR5 up-regulation and sensitization to TRAIL-induced apoptosis instigated by 6-DG were not observed in normal MDCK cells. Taken together, these data suggested that in addition to the mitochondrial- and Fas receptor-mediated apoptotic pathways involved, ROS-dependent and p53-regulated DR5 expression was also demonstrated to play a pivotal role in the synergistic enhancement of TRAIL-induced apoptosis instigated by 6-DG in Hep G2 cells.
从姜科植物根茎中分离得到的化合物 6-去氢姜二酮（6-DG）具有抗癌作用，本研究旨在探讨其增强 TRAIL 诱导的人肝癌 Hep G2 细胞凋亡的作用及其机制。本研究首次证明，6-DG 诱导的细胞凋亡可能通过线粒体和 Fas 受体介导的途径执行。进一步的研究还表明，6-DG 可以增强 Hep G2 细胞对 TRAIL 诱导的凋亡的敏感性。6-DG 还上调 Ser-15 磷酸化并引发 p53 核转位。用 p53 小干扰 RNA 阻断 p53 表达可显著减弱 6-DG 诱导的 DR5 表达，从而使这些细胞对 TRAIL 诱导的凋亡产生抗性。6-DG 处理后 DR5 的表达伴随着细胞内活性氧（ROS）的产生。用 N-乙酰-L-半胱氨酸（NAC）预处理可减弱 6-DG 诱导的 DR5 表达并抑制 TRAIL 诱导的凋亡。与 Hep G2 细胞不同，6-DG 诱导的正常 MDCK 细胞中未观察到 DR5 上调和对 TRAIL 诱导的凋亡的敏感性增强。综上所述，这些数据表明，除了涉及的线粒体和 Fas 受体介导的凋亡途径外，ROS 依赖性和 p53 调节的 DR5 表达也被证明在 6-DG 增强 TRAIL 诱导的 Hep G2 细胞凋亡的协同作用中发挥关键作用。
