Vlasova, O.; Antonova, I.; Magomedova, K.; Osipova, A.; Shtompel, P.; Borunova, A.; Zabotina, T.; Belitsky, G.; Budunova, I.; Jordan, A.; Kirsanov, K.; Yakubovskaya, M. Interferon Signaling Activation and LINE1 Expression under Influence of Anticancer Plant Secondary Metabolites. Preprints2024, 2024100853. https://doi.org/10.20944/preprints202410.0853.v1
APA Style
Vlasova, O., Antonova, I., Magomedova, K., Osipova, A., Shtompel, P., Borunova, A., Zabotina, T., Belitsky, G., Budunova, I., Jordan, A., Kirsanov, K., & Yakubovskaya, M. (2024). Interferon Signaling Activation and LINE1 Expression under Influence of Anticancer Plant Secondary Metabolites. Preprints. https://doi.org/10.20944/preprints202410.0853.v1
Chicago/Turabian Style
Vlasova, O., Kirill Kirsanov and Marianna Yakubovskaya. 2024 "Interferon Signaling Activation and LINE1 Expression under Influence of Anticancer Plant Secondary Metabolites" Preprints. https://doi.org/10.20944/preprints202410.0853.v1
Abstract
Previously we discovered that among 15 DNA-binding plant secondary metabolites (PSMs) possessing anticancer activity, 11 compounds cause depletion of the linker histones H1.2 and/or H1.4 from chromatin fraction. Chromatin remodeling or multiH1 knocking-down is known to promote the upregulation of repetitive elements, ultimately triggering an interferon response. Herein, using HeLa cells and applying fluorescent reporter assay with flow cytometry and quantitave RT-PCR, we found that among PSMs depleting linker histones, 8 compounds significantly activate type I interferon signaling pathway. Out of these compounds resveratrol, berberine, genistein, delphinidin, naringenin and curcumin also caused LINE1 expression detected by quantitate RT-PCR and by immunefluorescent staining analysis of ORF1 LINE1 and γ-H2AX. Fisetin and quercetin, which also induced linker histone depletion, significantly activated only type I interferon signaling, but not LINE1 expression. Curcumin, sanguinarine and kaempferol, causing depletion of the linker histone H1.4 more intensively respectively to H1.2, activate interferon signaling less intensively without any changes of LINE1 expression. For 4 PSMs, which did not cause linker histone depletion, we did not observe effects of interest. Thus, we have shown for the first time that activation of type I interferon signaling accompanies chromatin remodeling caused by PSMs, and LINE1 expression often impacts this activation.
Keywords
plant secondary metabolites; plant polyphenols; phytochemicals; DNA-binding compounds; anticancer effects; chromatin structure; linker histone depletion; type I interferon signaling; LINE1 transcription; double-stranded DNA ends
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
