Skip to main content

Research Repository

Advanced Search

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

Synthetic Diphenylacetylene-Based Retinoids Induce DNA Damage in Chinese Hamster Ovary Cells without Altering Viability Thumbnail


Authors

Lina Hudhud

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 Mar 28, 2024
Journal Molecules
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 27
Issue 3
Article Number 977
DOI https://doi.org/10.3390/molecules27030977

Files

Published Journal Article (1.6 Mb)
PDF

Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

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.





You might also like



Downloadable Citations