Assessing light-independent effects of hypericin on cell viability, ultrastructure and metabolism in human glioma and endothelial cells. (April 2017)

• Record Type: Journal Article
• Authors: Huntosova, Veronika; Novotova, Marta; Nichtova, Zuzana; Balogova, Lucia; Maslanakova, Maria; Petrovajova, Dana; Stroffekova, Katarina
• Is Part Of: Toxicology in vitro. Volume 40(2017)
• Page Start: 184
• Page End: 195
• Publication Date: 2017-04
• Subjects: ROS reactive oxygen species -- PDT photodynamic therapy -- Hyp hypericin -- HypPDT hypericin triggered PDT -- ER endoplasmic reticulum -- GA Golgi apparatus -- PS photosensitizer -- ECs endothelial cells; Oxidative stress -- Mitochondria -- Hypericin -- Cell death -- Cell metabolism; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2017.01.005
• Languages: English
• ISSNs: 0887-2333

Abstract

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. Graphical abstract: Highlights: Hypericin results in the swelling of the Golgi apparatus. Hypericin causes fragmentation and decreased ER granularity. Hypericin increases ROS production in glioma and endothelial cells. Hypericin attenuates cell metabolism more in glioma than in endothelial cells. Hypericin results in apoptosis more in endothelial than in glioma cells.