Cargando…

Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles

In the present work, we investigated the dark and photoinduced cytotoxic activity of the new chlorophyll-a derivatives which contain the substituents of oligoethylene glycol on the periphery of their macrocycles. These compounds were tested using human cell lines to estimate their potential as photo...

Descripción completa

Detalles Bibliográficos
Autores principales: Pylina, Yana I., Shadrin, Dmitry M., Shevchenko, Oksana G., Startseva, Olga M., Velegzhaninov, Igor O., Belykh, Dmitry V., Velegzhaninov, Ilya O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297737/
https://www.ncbi.nlm.nih.gov/pubmed/28067798
http://dx.doi.org/10.3390/ijms18010103
_version_ 1782505771762712576
author Pylina, Yana I.
Shadrin, Dmitry M.
Shevchenko, Oksana G.
Startseva, Olga M.
Velegzhaninov, Igor O.
Belykh, Dmitry V.
Velegzhaninov, Ilya O.
author_facet Pylina, Yana I.
Shadrin, Dmitry M.
Shevchenko, Oksana G.
Startseva, Olga M.
Velegzhaninov, Igor O.
Belykh, Dmitry V.
Velegzhaninov, Ilya O.
author_sort Pylina, Yana I.
collection PubMed
description In the present work, we investigated the dark and photoinduced cytotoxic activity of the new chlorophyll-a derivatives which contain the substituents of oligoethylene glycol on the periphery of their macrocycles. These compounds were tested using human cell lines to estimate their potential as photosensitizers for photodynamic therapy of cancer. It was shown that all the tested compounds have expressed photoinduced cytotoxic activity in vitro. Detailed study of the biological activity of one of the most perspective compound in this series—pyropheophorbide-a 17-diethylene glycol ester (Compound 21) was performed. This new compound is characterized by lower dark cytotoxicity and higher photoinduced cytotoxicity than previously described in a similar compound (DH-I-180-3) and clinically used Photolon(TM). Using fluorescent microscopy, it was shown that Compound 21 quickly penetrates the cells. Analysis of caspase-3 activity indicated an apoptosis induction 40 min after exposure to red light (λ = 660 nm). The induction of DNA damages and apoptosis was shown using Comet assay. The results of expression analysis of the stress-response genes indicate an activation of the genes which control the cell cycle and detoxification of the free radicals after an exposure of HeLa cells to Compound 21 and to red light. High photodynamic activity of this compound and the ability to oxidize biomolecules was demonstrated on nuclear-free mice erythrocytes. In addition, it was shown that Compound 21 is effectively activated with low energy 700 nm light, which can penetrate deep into the tissue. Thus, Compound 21 is a prospective substance for development of the new drugs for photodynamic therapy of cancer.
format Online
Article
Text
id pubmed-5297737
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-52977372017-02-10 Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles Pylina, Yana I. Shadrin, Dmitry M. Shevchenko, Oksana G. Startseva, Olga M. Velegzhaninov, Igor O. Belykh, Dmitry V. Velegzhaninov, Ilya O. Int J Mol Sci Article In the present work, we investigated the dark and photoinduced cytotoxic activity of the new chlorophyll-a derivatives which contain the substituents of oligoethylene glycol on the periphery of their macrocycles. These compounds were tested using human cell lines to estimate their potential as photosensitizers for photodynamic therapy of cancer. It was shown that all the tested compounds have expressed photoinduced cytotoxic activity in vitro. Detailed study of the biological activity of one of the most perspective compound in this series—pyropheophorbide-a 17-diethylene glycol ester (Compound 21) was performed. This new compound is characterized by lower dark cytotoxicity and higher photoinduced cytotoxicity than previously described in a similar compound (DH-I-180-3) and clinically used Photolon(TM). Using fluorescent microscopy, it was shown that Compound 21 quickly penetrates the cells. Analysis of caspase-3 activity indicated an apoptosis induction 40 min after exposure to red light (λ = 660 nm). The induction of DNA damages and apoptosis was shown using Comet assay. The results of expression analysis of the stress-response genes indicate an activation of the genes which control the cell cycle and detoxification of the free radicals after an exposure of HeLa cells to Compound 21 and to red light. High photodynamic activity of this compound and the ability to oxidize biomolecules was demonstrated on nuclear-free mice erythrocytes. In addition, it was shown that Compound 21 is effectively activated with low energy 700 nm light, which can penetrate deep into the tissue. Thus, Compound 21 is a prospective substance for development of the new drugs for photodynamic therapy of cancer. MDPI 2017-01-05 /pmc/articles/PMC5297737/ /pubmed/28067798 http://dx.doi.org/10.3390/ijms18010103 Text en © 2017 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pylina, Yana I.
Shadrin, Dmitry M.
Shevchenko, Oksana G.
Startseva, Olga M.
Velegzhaninov, Igor O.
Belykh, Dmitry V.
Velegzhaninov, Ilya O.
Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles
title Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles
title_full Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles
title_fullStr Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles
title_full_unstemmed Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles
title_short Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles
title_sort dark and photoinduced cytotoxic activity of the new chlorophyll-a derivatives with oligoethylene glycol substituents on the periphery of their macrocycles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297737/
https://www.ncbi.nlm.nih.gov/pubmed/28067798
http://dx.doi.org/10.3390/ijms18010103
work_keys_str_mv AT pylinayanai darkandphotoinducedcytotoxicactivityofthenewchlorophylladerivativeswitholigoethyleneglycolsubstituentsontheperipheryoftheirmacrocycles
AT shadrindmitrym darkandphotoinducedcytotoxicactivityofthenewchlorophylladerivativeswitholigoethyleneglycolsubstituentsontheperipheryoftheirmacrocycles
AT shevchenkooksanag darkandphotoinducedcytotoxicactivityofthenewchlorophylladerivativeswitholigoethyleneglycolsubstituentsontheperipheryoftheirmacrocycles
AT startsevaolgam darkandphotoinducedcytotoxicactivityofthenewchlorophylladerivativeswitholigoethyleneglycolsubstituentsontheperipheryoftheirmacrocycles
AT velegzhaninovigoro darkandphotoinducedcytotoxicactivityofthenewchlorophylladerivativeswitholigoethyleneglycolsubstituentsontheperipheryoftheirmacrocycles
AT belykhdmitryv darkandphotoinducedcytotoxicactivityofthenewchlorophylladerivativeswitholigoethyleneglycolsubstituentsontheperipheryoftheirmacrocycles
AT velegzhaninovilyao darkandphotoinducedcytotoxicactivityofthenewchlorophylladerivativeswitholigoethyleneglycolsubstituentsontheperipheryoftheirmacrocycles