白藜芦醇诱导的人伯基特淋巴瘤细胞毒性与未折叠蛋白反应有关。
Resveratrol-induced cytotoxicity in human Burkitt's lymphoma cells is coupled to the unfolded protein response.
机构信息
Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110001, China.
出版信息
BMC Cancer. 2010 Aug 20;10:445. doi: 10.1186/1471-2407-10-445.
BACKGROUND
Resveratrol (RES), a natural phytoalexin found at high levels in grapes and red wine, has been shown to induce anti-proliferation and apoptosis of human cancer cell lines. However, the underlying molecular mechanisms are at present only partially understood.
METHOD
The effects of RES on activation of unfolded protein responses (UPR) were evaluated using Western blotting, semi-quantitative and real-time RT-PCR. Cell death was evaluated using Annexin V/PI staining and subsequent FACS.
RESULTS
Similar as tunicamycin, treatment with RES lead to the activation of all 3 branches of the UPR, with early splicing of XBP-1 indicative of IRE1 activation, phosphorylation of eIF2alpha consistent with ER resident kinase (PERK) activation, activating transcription factor 6 (ATF6) splicing, and increase in expression levels of the downstream molecules GRP78/BiP, GRP94 and CHOP/GADD153 in human Burkitt's lymphoma Raji and Daudi cell lines. RES was shown to induce cell death, which could be attenuated by thwarting upregulation of CHOP.
CONCLUSIONS
Our data suggest that activation of the apoptotic arm of the UPR and its downstream effector CHOP/GADD153 is involved, at least in part, in RES-induced apoptosis in Burkitt's lymphoma cells.
背景
白藜芦醇（RES）是一种天然植物抗毒素，在葡萄和红酒中含量很高，已被证明能诱导人类癌细胞系的抗增殖和凋亡。然而，目前对其潜在的分子机制还只是部分了解。
方法
用 Western blot、半定量和实时 RT-PCR 评估 RES 对未折叠蛋白反应（UPR）激活的影响。用 Annexin V/PI 染色和随后的 FACS 评估细胞死亡。
结果
与衣霉素相似，RES 的处理导致 UPR 的 3 个分支都被激活，XBP-1 的早期剪接表明 IRE1 的激活，eIF2alpha 的磷酸化与内质网驻留激酶（PERK）的激活一致，激活转录因子 6（ATF6）的剪接，以及下游分子 GRP78/BiP、GRP94 和 CHOP/GADD153 的表达水平在人 Burkitt 淋巴瘤 Raji 和 Daudi 细胞系中增加。RES 被证明能诱导细胞死亡，而 CHOP 的上调受阻可减轻这种诱导。
结论
我们的数据表明，UPR 的凋亡分支及其下游效应分子 CHOP/GADD153 的激活至少部分参与了 RES 诱导 Burkitt 淋巴瘤细胞凋亡。
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