title: Assessing light-independent effects of hypericin on cell viability, ultrastructure and metabolism in human glioma and endothelial cells.
abstract: Cell exposure to light-independent effects of photosensitizers (PS) used in PDT is clinically relevant when PS affect the pro-apoptotic cascade. In many malignant cells, Hypericin (Hyp) has PS displayed light-dependent anti-proliferative and cytotoxic effects with no cytotoxicity in the dark. Recent studies have shown that Hyp also exhibited light-independent cytotoxic effects in a wide range of concentrations. The molecular mechanisms underlying Hyp light-independent (dark) toxicity may be due to its interaction with different molecules at the Hyp accumulation sites including mitochondria, and these mechanisms are not understood in detail. Here, we demonstrate that in human glioma and endothelial cells, Hyp displayed light-independent effects at several sub-cellular levels (ultrastructure, mitochondria function and metabolism, and protein synthesis). Taking together previously published and our present results, the findings strongly suggest that Hyp light independent effects: (i) depend on the cell type and metabolism; (ii) underlying molecular mechanisms are due to Hyp interaction with the multiple target molecules including Bcl2 family of proteins. In addition, the findings suggest that Hyp without illumination can be explored as an adjuvant therapeutic drug in combination with chemo- or radiation cancer therapy.
authors.affiliation: Center for Interdisciplinary Biosciences, PJ Safarik University in Kosice, Slovakia.
authors.forename: Veronika
authors.initials: V
authors.lastname: Huntosova
authors.affiliation: Department of Muscle Cell Research, Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Science, Bratislava, Slovakia.
authors.forename: Marta
authors.initials: M
authors.lastname: Novotova
authors.affiliation: Department of Muscle Cell Research, Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Science, Bratislava, Slovakia.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Nichtova
authors.affiliation: Department of Biophysics, Faculty of Natural Sciences, PJ Safarik University, Jesenna 5, Kosice, Slovakia.
authors.forename: Lucia
authors.initials: L
authors.lastname: Balogova
authors.affiliation: Department of Biophysics, Faculty of Natural Sciences, PJ Safarik University, Jesenna 5, Kosice, Slovakia.
authors.forename: Maria
authors.initials: M
authors.lastname: Maslanakova
authors.affiliation: Department of Biophysics, Faculty of Natural Sciences, PJ Safarik University, Jesenna 5, Kosice, Slovakia.
authors.forename: Dana
authors.initials: D
authors.lastname: Petrovajova
authors.affiliation: Department of Biophysics, Faculty of Natural Sciences, PJ Safarik University, Jesenna 5, Kosice, Slovakia. Electronic address: katarina.stroffekova@upjs.sk.
authors.forename: Katarina
authors.initials: K
authors.lastname: Stroffekova
mesh_terms: D000873:Anthracenes; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005910:Glioma / Q000378:metabolism / Q000648:ultrastructure; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008027:Light; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010569:Perylene / Q000031:analogs & derivatives* / Q000633:toxicity; D017319:Photosensitizing Agents / Q000633:toxicity*
chemical_list: D000873:Anthracenes; D017319:Photosensitizing Agents; D010569:Perylene; C004965:hypericin
keywords: Cell death; Cell metabolism; Hypericin; Mitochondria; Oxidative stress