Meta-stable state photoacid containing β-estradiol fragment with photomodulated biological activity and anti-cancer stem cells properties.

Autor: Ozhogin IV; Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., 344090 Rostov-on-Don, Russian Federation. Electronic address: iozhogin@sfedu.ru., Zolotukhin PV; Bioinn, LLC, 37 Sodruzhestva st., 344103 Rostov-on-Don, Russian Federation., Makarova NI; Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., 344090 Rostov-on-Don, Russian Federation., Rostovtseva IA; Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., 344090 Rostov-on-Don, Russian Federation., Pugachev AD; Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., 344090 Rostov-on-Don, Russian Federation., Kozlenko AS; Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., 344090 Rostov-on-Don, Russian Federation., Belanova AA; Bioinn, LLC, 37 Sodruzhestva st., 344103 Rostov-on-Don, Russian Federation., Borodkin GS; Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., 344090 Rostov-on-Don, Russian Federation., Dorogan IV; Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., 344090 Rostov-on-Don, Russian Federation., Metelitsa AV; Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., 344090 Rostov-on-Don, Russian Federation.
Jazyk: angličtina
Zdroj: Journal of photochemistry and photobiology. B, Biology [J Photochem Photobiol B] 2024 Aug; Vol. 257, pp. 112964. Date of Electronic Publication: 2024 Jun 26.
DOI: 10.1016/j.jphotobiol.2024.112964
Abstrakt: Photopharmacology is a young and rapidly developing field of research that offers significant potential for new insights into targeted therapy. While it primarily focuses on cancer treatment, it also holds promise for other diseases. The key feature of photopharmacological agents is the presence of a photosensitive and biologically active component in the same molecule. In our current study, we synthesized a spiropyran-based meta-stable state photoacid containing a fragment of β-estradiol. This compound exhibits negative photochromism and photocontrolled fluorescence under visible-light irradiation due to the initial stabilization of its self-protonated form in solution. We conducted comprehensive biological studies on the HeLa cells model to assess the short- and long-term cytotoxicity of the photoacid, its metabolic effects, its influence on signaling and epithelial-mesenchymal transition super-system pathways, and the proportion of the population enriched with cancer stem cells. Our findings reveal that this derivative demonstrates low cytotoxicity to HeLa cells, yet it is capable of dramatically reducing malignant cells side population enriched in cancer stem cells. Additionally, appropriate structural modification lead to an increase in some other biological effects compared to β-estradiol. In particular, our substance possesses rare properties of AP-1 suppression and demonstrates some pro-oxidant and metabolic effects, which can be regulated by visible light irradiation. As a result, the new estradiol-based photoacid may be considered a promising multi-acting photopharmacological agent for the next-generation anti-cancer research & development.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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