Lina Hudhud
Synthetic Diphenylacetylene-Based Retinoids Induce DNA Damage in Chinese Hamster Ovary Cells without Altering Viability
Hudhud, Lina; Chisholm, David R.; Whiting, Andrew; Steib, Anita; Pohóczky, Krisztina; Kecskés, Angéla; Szőke, Éva; Helyes, Zsuzsanna
Authors
David Chisholm d.r.chisholm@durham.ac.uk
PGR Student Doctor of Philosophy
Professor Andrew Whiting andy.whiting@durham.ac.uk
Emeritus Professor
Anita Steib
Krisztina Pohóczky
Angéla Kecskés
Éva Szőke
Zsuzsanna Helyes
Abstract
All-trans-retinoic acid (ATRA), the active metabolite of vitamin A, plays a pivotal role in cell differentiation, proliferation and embryonic development. It is an effective therapy for dermatological disorders and malignancies. ATRA is prone to isomerization and oxidation, which can affect its activity and selectivity. Novel diphenylacetylene-based ATRA analogues with increased stability can help to overcome these problems and may offer significant potential as therapeutics for a variety of cancers and neurodegenerative diseases, including amyotrophic lateral sclerosis. Here, we investigated the effects of these retinoids on cell viability and genotoxicity in the widely used model system of the rapidly proliferating Chinese hamster ovary cell line. DC360 is a fluorescent ATRA analogue and DC324 is a non-active derivative of DC360. EC23, DC525, DC540, DC645, and DC712 are promising analogues with increased bioactivity. The cytotoxic activity of the compounds was evaluated by ATP assay and DNA damage was tested by comet assay. No cytotoxicity was observed in the 10−6–10−5 M concentration range. All compounds induced DNA migration similar to ATRA, but DC324, DC360 and EC23 did so to a greater extent, particularly at higher concentrations. We believe that retinoid receptor-independent genotoxicity is a general characteristic of these compounds; however, further studies are needed to identify the molecular mechanisms and understand their complex biological functions.
Citation
Hudhud, L., Chisholm, D. R., Whiting, A., Steib, A., Pohóczky, K., Kecskés, A., …Helyes, Z. (2022). Synthetic Diphenylacetylene-Based Retinoids Induce DNA Damage in Chinese Hamster Ovary Cells without Altering Viability. Molecules, 27(3), Article 977. https://doi.org/10.3390/molecules27030977
Journal Article Type | Article |
---|---|
Acceptance Date | Jan 26, 2022 |
Online Publication Date | Feb 1, 2022 |
Publication Date | Feb 1, 2022 |
Deposit Date | Feb 1, 2022 |
Publicly Available Date | Feb 1, 2022 |
Journal | Molecules |
Publisher | MDPI |
Peer Reviewed | Peer Reviewed |
Volume | 27 |
Issue | 3 |
Article Number | 977 |
DOI | https://doi.org/10.3390/molecules27030977 |
Public URL | https://durham-repository.worktribe.com/output/1216398 |
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Copyright Statement
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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