双去甲氧基姜黄素可能通过p53/Bcl-2途径增强X射线诱导的细胞凋亡。
Bisdemethoxycurcumin enhances X-ray-induced apoptosis possibly through p53/Bcl-2 pathway.
作者信息
Enomoto Atsushi, Yamada Junko, Morita Akinori, Miyagawa Kiyoshi
机构信息
Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku Tokyo 113-0033, Japan.
Radiation Safety Office, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku Tokyo 113-0033, Japan.
出版信息
Mutat Res Genet Toxicol Environ Mutagen. 2017 Mar;815:1-5. doi: 10.1016/j.mrgentox.2016.12.005. Epub 2017 Jan 11.
Bisdemethoxycurcumin (BDMC), which is isolated from the rhizomes of Curcuma longa, has anti-inflammatory and anti-carcinogenic activities. Here we found that BDMC enhanced X-ray-induced apoptosis in human T-cell leukemia MOLT-4 cells. Knockdown of p53 significantly attenuated the radiosensitizing effect of BDMC. However, BDMC did not enhance X-ray-mediated activation of the p53 signaling pathway via p53's transactivation or mitochondrial translocation. On the other hand, BDMC promoted the X-ray-induced dephosphorylation at Ser 70 in Bcl-2's flexible loop regulatory domain and Bcl-2 binding to p53. Overexpressing Bcl-2 completely blocked the BDMC's radiosensitization effect. Our results indicate that BDMC stimulates the dephosphorylation and p53-binding activity of Bcl-2 and suggest that BDMC may induce a neutralization of Bcl-2's anti-apoptotic function, thereby enhancing X-ray-induced apoptosis.
双去甲氧基姜黄素（BDMC）是从姜黄根茎中分离出来的，具有抗炎和抗癌活性。在此我们发现，BDMC增强了X射线诱导的人T细胞白血病MOLT-4细胞凋亡。敲低p53可显著减弱BDMC的放射增敏作用。然而，BDMC并未通过p53的反式激活或线粒体易位增强X射线介导的p53信号通路激活。另一方面，BDMC促进了X射线诱导的Bcl-2柔性环调节结构域中Ser 70位点的去磷酸化以及Bcl-2与p53的结合。过表达Bcl-2完全阻断了BDMC的放射增敏作用。我们的结果表明，BDMC刺激了Bcl-2的去磷酸化和p53结合活性，并提示BDMC可能诱导Bcl-2抗凋亡功能的中和，从而增强X射线诱导的凋亡。
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