Zinc Supplementation Enhances the Pro-Death Function of UPR in Lymphoma Cells Exposed to Radiation

Biology

Luisa Guttieri¹  Maria Saveria Gilardini Montani²  Mara Cirone²  Roberta Gonnella²  Roberta Santarelli²  Gabriella D’Orazi³  Erica Bassetti⁴ 

[1] Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy;Department of Experimental Medicine, “Sapienza” University of Rome, 00161 Rome, Italy;Department of Neurosciences, Imaging and Clinical Sciences, University “G. D’Annunzio” Chieti, 66013 Chieti, Italy;Department of Radiological, Oncological and Pathological Sciences, “Sapienza” University of Rome, 00161 Rome, Italy;

关键词: ER stress/UPR;    DDR;    CHOP;    ERK1/2;    p53;    PEL;   

DOI  :  10.3390/biology11010132

来源: DOAJ

【 摘 要 】

We have previously shown that Zinc supplementation triggered ER stress/UPR in cancer cells undergoing treatment by genotoxic agents, reactivated wtp53 in cancer cells harboring mutant p53 (mutp53) and potentiated the activity of wtp53 in those carrying wtp53. In this study, we used Zinc chloride alone or in combination with 2 Gy radiation to treat Primary Effusion Lymphoma (PEL) cells, an aggressive B-cell lymphoma associated with KSHV that harbors wt or partially functioning p53. We found that Zinc triggered a mild ER stress/UPR in these lymphoma cells and activated ERK1/2, molecule known to sustain cell survival in the course of UPR activation. In combination with radiations, Zinc triggered a stronger p53 activation that counteracted its mediated ERK1/2 phosphorylation, further upregulating the UPR molecule CHOP and promoting cell death. These data suggest that Zinc supplementation could be a promising strategy to reduce the doses of radiation and possibly of other DNA-damaging agents to obtain an efficient capacity to induce lymphoma cell death.

【 授权许可】

Unknown