title: Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles.
abstract: 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 (Compound21) 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 Compound21quickly 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 Compound21and 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 Compound21is effectively activated with low energy 700 nm light, which can penetrate deep into the tissue. Thus, Compound21is a prospective substance for development of the new drugs for photodynamic therapy of cancer.
authors.affiliation: Institute of Biology of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, Russia. yanapylina@yandex.ru.
authors.forename: Yana I
authors.initials: YI
authors.lastname: Pylina
authors.affiliation: Institute of Biology of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, Russia. shdimas@yandex.ru.
authors.forename: Dmitry M
authors.initials: DM
authors.lastname: Shadrin
authors.affiliation: Institute of Biology of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, Russia. microtus69@mail.ru.
authors.forename: Oksana G
authors.initials: OG
authors.lastname: Shevchenko
authors.affiliation: Institute of Chemistry of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, Russia. om_smirnova@mail.ru.
authors.forename: Olga M
authors.initials: OM
authors.lastname: Startseva
authors.affiliation: Institute of Geology of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, Russia. saturn_vio@mail.ru.
authors.forename: Igor O
authors.initials: IO
authors.lastname: Velegzhaninov
authors.affiliation: Institute of Chemistry of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, Russia. belykh-dv@mail.ru.
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Belykh
authors.affiliation: Institute of Biology of Komi Science Centre of Ural Branch of RAS, Syktyvkar 167982, Russia. vellio@yandex.ru.
authors.forename: Ilya O
authors.initials: IO
authors.lastname: Velegzhaninov
mesh_terms: D000072283:A549 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002735:Chlorophyllides; D020552:Comet Assay; D004249:DNA Damage; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D057809:HEK293 Cells; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008027:Light; D051379:Mice; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002735:Chlorophyllides; C000607508:DH-I-180-3; D017319:Photosensitizing Agents; D011166:Porphyrins; C000617855:pyropheophorbide-a 17-diethylene glycol ester; D002734:Chlorophyll; D011092:Polyethylene Glycols; C062985:phytochlorin
keywords: HeLa; chlorophyll-a derivatives; cytotoxic activity; oligoethylene glycol substituent; photodynamic therapy; photohemolysis; photosensitizer