Document Type

Article

Publication Date

2018

Publication Title

Oncotarget

Volume

9

Issue

27

Pages

18665-18681

DOI

10.18632/oncotarget.24816

Abstract

Cytosolic DNA sensors are a subgroup of pattern recognition receptors (PRRs) and are activated by the abnormal presence of the DNA in the cytosol. Their activation leads to the upregulation of pro-inflammatory cytokines and chemokines and can also induce cell death. The presence of cytosolic DNA sensors and inflammatory cytokines in TS/A murine mammary adenocarcinoma and WEHI 164 fibrosarcoma cells was demonstrated using real time reverse transcription polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbent assay (ELISA). After electrotransfer of plasmid DNA (pDNA) using two pulse protocols, the upregulation of DNA-depended activator of interferon regulatory factor or Z-DNA binding protein 1 (DAI/ZBP1), DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 (DDX60) and interferon-inducible protein 204 (p204) mRNAs was observed in both tumor cell lines, but their expression was pulse protocol dependent. A decrease in cell survival was also observed; it was cell type, DNA concentration and pulse protocol dependent. Furthermore, the different protocols of electrotransfer led to different cell death outcomes, necrosis and apoptosis, as indicated by an annexin V and 7AAD assays. The obtained data provide new insights on the presence of cytosolic DNA sensors in tumor cells and the activation of different types of cells death after electrotransfer of pDNA. These observations have important implications on the planning of gene therapy or DNA vaccination protocols.

Comments

This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Copyright: Znidar et al.

Original Publication Citation

Znidar, K., Bosnjak, M., Semenova, N., Pakhomova, O., Heller, L., & Cemazar, M. (2018). Tumor cell death after electrotransfer of plasmid DNA is associated with cytosolic DNA sensor upregulation. Oncotarget, 9(27), 18665-18681. doi:10.18632/oncotarget.24816

ORCID

0000-0003-4950-4130 (Pakhomova, O.), 0000-0001-8084-0787 (Heller, L.)

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