Zinc Supplementation Enhances the Pro-Death Function of UPR in Lymphoma Cells Exposed to Radiation
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 alo...
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MDPI AG
2022-01-01
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| Online Access: | https://www.mdpi.com/2079-7737/11/1/132 |
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| author | Roberta Gonnella Luisa Guttieri Maria Saveria Gilardini Montani Roberta Santarelli Erica Bassetti Gabriella D’Orazi Mara Cirone |
| author_facet | Roberta Gonnella Luisa Guttieri Maria Saveria Gilardini Montani Roberta Santarelli Erica Bassetti Gabriella D’Orazi Mara Cirone |
| author_sort | Roberta Gonnella |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T01:53:19Z |
| format | Article |
| id | doaj.art-cb1bfdb101f94924a0ea1c325f1fb297 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T01:53:19Z |
| publishDate | 2022-01-01 |
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| record_format | Article |
| series | Biology |
| spelling | doaj.art-cb1bfdb101f94924a0ea1c325f1fb2972023-11-23T13:01:46ZengMDPI AGBiology2079-77372022-01-0111113210.3390/biology11010132Zinc Supplementation Enhances the Pro-Death Function of UPR in Lymphoma Cells Exposed to RadiationRoberta Gonnella0Luisa Guttieri1Maria Saveria Gilardini Montani2Roberta Santarelli3Erica Bassetti4Gabriella D’Orazi5Mara Cirone6Department of Experimental Medicine, “Sapienza” University of Rome, 00161 Rome, ItalyDepartment of Clinical and Molecular Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, 00161 Rome, ItalyDepartment of Radiological, Oncological and Pathological Sciences, “Sapienza” University of Rome, 00161 Rome, ItalyDepartment of Neurosciences, Imaging and Clinical Sciences, University “G. D’Annunzio” Chieti, 66013 Chieti, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, 00161 Rome, ItalyWe 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.https://www.mdpi.com/2079-7737/11/1/132ER stress/UPRDDRCHOPERK1/2p53PEL |
| spellingShingle | Roberta Gonnella Luisa Guttieri Maria Saveria Gilardini Montani Roberta Santarelli Erica Bassetti Gabriella D’Orazi Mara Cirone Zinc Supplementation Enhances the Pro-Death Function of UPR in Lymphoma Cells Exposed to Radiation Biology ER stress/UPR DDR CHOP ERK1/2 p53 PEL |
| title | Zinc Supplementation Enhances the Pro-Death Function of UPR in Lymphoma Cells Exposed to Radiation |
| title_full | Zinc Supplementation Enhances the Pro-Death Function of UPR in Lymphoma Cells Exposed to Radiation |
| title_fullStr | Zinc Supplementation Enhances the Pro-Death Function of UPR in Lymphoma Cells Exposed to Radiation |
| title_full_unstemmed | Zinc Supplementation Enhances the Pro-Death Function of UPR in Lymphoma Cells Exposed to Radiation |
| title_short | Zinc Supplementation Enhances the Pro-Death Function of UPR in Lymphoma Cells Exposed to Radiation |
| title_sort | zinc supplementation enhances the pro death function of upr in lymphoma cells exposed to radiation |
| topic | ER stress/UPR DDR CHOP ERK1/2 p53 PEL |
| url | https://www.mdpi.com/2079-7737/11/1/132 |
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