Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Ectoine Globally Hypomethylates DNA in Skin Cells and Suppresses Cancer Proliferation

Majjid A Qaria
ORCID logo ,
Chunyan Xu
,
Hu Ran
,
Roua A. Alsubki
ORCID logo ,
Mohamed Yassin Ali
ORCID logo ,
Sethupathy Sivasamy
ORCID logo ,
Kotb A. Attia
* ORCID logo ,
Daochen Zhu
*
Version 1 : Received: 3 August 2023 / Approved: 4 August 2023 / Online: 7 August 2023 (09:58:44 CEST)

A peer-reviewed article of this Preprint also exists.

Qaria, M.A.; Xu, C.; Hu, R.; Alsubki, R.A.; Ali, M.Y.; Sivasamy, S.; Attia, K.A.; Zhu, D. Ectoine Globally Hypomethylates DNA in Skin Cells and Suppresses Cancer Proliferation. Marine Drugs 2023, 21, 621, doi:10.3390/md21120621. Qaria, M.A.; Xu, C.; Hu, R.; Alsubki, R.A.; Ali, M.Y.; Sivasamy, S.; Attia, K.A.; Zhu, D. Ectoine Globally Hypomethylates DNA in Skin Cells and Suppresses Cancer Proliferation. Marine Drugs 2023, 21, 621, doi:10.3390/md21120621.

Abstract

Epigenetic modifications, mainly aberrant DNA methylation, have been shown to silence the ex-pression of genes involved in epigenetic diseases, including cancer suppression genes. Almost all conventional cancer therapeutic agents, such as the DNA hypomethylation drug, 5-aza-2-deoxycytidine, have insurmountable side effects. To investigate the role of ectoine in skin cell DNA methylation and cancer cell proliferation, comprehensive methylome sequence analysis, 5-methyl cytosine (5mC) analysis, proliferation and tumorigenicity assays, and DNA methyla-tion-related gene and marker analysis were performed. The results showed that ectoine hypo-methylation in skin cells, especially in the CpG island (CGIs) element and 5mC, was significantly reduced. Moreover, ectoine mildly inhibited skin cell proliferation, but did not induce tumorigenicity in HaCaT cells injected into athymic nude mice. HaCaT cells treated with ectoine for 24 weeks modulated the mRNA expression levels of Dnmt1, Dnmt3a, Dnmt3b, Dnmt3i, Hdac1, Hdac2, Kdm3a, Mettl3, Mettl14, Igf2, Snrpn, and Mest. Overall, ectoine, an excellent DNA protectant, mildly de-methylates DNA in skin cells, modulates the expression of methylation-related genes, and reduces cell proliferation. This evidence suggests that ectoine is a potential anti-aging agent that prevents DNA hypermethylation and subsequently activates cancer-suppressing genes.

Keywords

ectoine; epigenetic modifications; DNA hypomethylation; skin cells; tumorigenicity; cell proliferation; DNMTs; anti-ageing; cancer

Subject

Medicine and Pharmacology, Medicine and Pharmacology

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.

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