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...
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doaj-9453ab7ca25e46b49d28daeeba7ec3452020-11-25T01:12:09ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-01-0118110310.3390/ijms18010103ijms18010103Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their MacrocyclesYana I. Pylina0Dmitry M. Shadrin1Oksana G. Shevchenko2Olga M. Startseva3Igor O. Velegzhaninov4Dmitry V. Belykh5Ilya O. Velegzhaninov6Institute of Biology of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, RussiaInstitute of Biology of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, RussiaInstitute of Biology of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, RussiaInstitute of Chemistry of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, RussiaInstitute of Geology of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, RussiaInstitute of Chemistry of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, RussiaInstitute of Biology of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, RussiaIn 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 PhotolonTM. 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.http://www.mdpi.com/1422-0067/18/1/103photosensitizerphotodynamic therapyHeLaphotohemolysischlorophyll-a derivativesoligoethylene glycol substituentcytotoxic activity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yana I. Pylina Dmitry M. Shadrin Oksana G. Shevchenko Olga M. Startseva Igor O. Velegzhaninov Dmitry V. Belykh Ilya O. Velegzhaninov |
spellingShingle |
Yana I. Pylina Dmitry M. Shadrin Oksana G. Shevchenko Olga M. Startseva Igor O. Velegzhaninov Dmitry V. Belykh Ilya O. Velegzhaninov Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles International Journal of Molecular Sciences photosensitizer photodynamic therapy HeLa photohemolysis chlorophyll-a derivatives oligoethylene glycol substituent cytotoxic activity |
author_facet |
Yana I. Pylina Dmitry M. Shadrin Oksana G. Shevchenko Olga M. Startseva Igor O. Velegzhaninov Dmitry V. Belykh Ilya O. Velegzhaninov |
author_sort |
Yana I. Pylina |
title |
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_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_sort |
dark and photoinduced cytotoxic activity of the new chlorophyll-a derivatives with oligoethylene glycol substituents on the periphery of their macrocycles |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2017-01-01 |
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 PhotolonTM. 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. |
topic |
photosensitizer photodynamic therapy HeLa photohemolysis chlorophyll-a derivatives oligoethylene glycol substituent cytotoxic activity |
url |
http://www.mdpi.com/1422-0067/18/1/103 |
work_keys_str_mv |
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