Resveratrol-induced cytotoxicity in human Burkitts lymphoma cells is coupled to the unfolded protein responseReportar como inadecuado




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BMC Cancer

, 10:445

First Online: 20 August 2010Received: 24 March 2010Accepted: 20 August 2010DOI: 10.1186-1471-2407-10-445

Cite this article as: Yan, Y., Gao, YY., Liu, BQ. et al. BMC Cancer 2010 10: 445. doi:10.1186-1471-2407-10-445

Abstract

BackgroundResveratrol 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.

MethodThe 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.

ResultsSimilar 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 eIF2α 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.

ConclusionsOur 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-10-445 contains supplementary material, which is available to authorized users.

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Autor: Ying Yan - Yan-Yan Gao - Bao-Qin Liu - Xiao-Fang Niu - Ying Zhuang - Hua-Qin Wang

Fuente: https://link.springer.com/







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