Hypericin-photodynamic therapy induces human umbilical vein endothelial cell apoptosis

• Published in: Scientific reports 2015-12, Vol.5 (1), p.18398, Article 18398
• Main Authors: Zhang, Qian, Li, Zhuo-heng, Li, Yuan-yuan, Shi, San-jun, Zhou, Shi-wen, Fu, Yuan-yuan, Zhang, Qing, Yang, Xue, Fu, Ruo-qiu, Lu, Lai-chun
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 13; 13/2; 13/21; 13/31; 38/77; 38/90; 631/80/82/23; 631/80/86/820; 82; 82/1; 82/80; 82/83; AKT protein; Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Blotting, Western; Caspase; Caspase 3 - genetics; Caspase 3 - metabolism; Cell activation; Cell Line; Cytokines - genetics; Cytokines - metabolism; Endothelial cells; Gene Expression - drug effects; Gene Expression - radiation effects; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - radiation effects; Humanities and Social Sciences; Humans; Hypericin; Inflammation; Light; Membrane Potential, Mitochondrial - drug effects; Membrane Potential, Mitochondrial - radiation effects; Mitochondria; multidisciplinary; Perylene - analogs & derivatives; Perylene - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Photochemotherapy - methods; Photodynamic therapy; Proto-Oncogene Proteins c-akt - metabolism; Radiation-Sensitizing Agents - pharmacology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Science; Signal Transduction - drug effects; Signal Transduction - radiation effects; Toxicity; Umbilical vein; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Wine
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep18398

The conventional photosensitizers used in photodynamic therapy (PDT), such as haematoporphyrin (HP), have not yet reached satisfactory therapeutic effects on port-wine stains (PWSs), due largely to the long-term dark toxicity. Previously we have showed that hypericin exhibited potent photocytotoxic effects on Roman chicken cockscomb model of PWSs. However, the molecular mechanism of hypericin-mediated photocytotoxicity remains unclear. In this study, we employed human umbilical vein endothelial cells (HUVECs) to investigate the hypericin-photolytic mechanism. Our study showed that hypericin-PDT induced reactive oxygen species (ROS), resulting in cell killings and an activation of the inflammatory response. Importantly, we have also discovered that photoactivated hypericin induced apoptosis by activating the mitochondrial caspase pathway and inhibiting the activation of the vascular endothelial growth factor-A (VEGF-A)-mediated PI3K/Akt pathway. Notably, we found that hypericin exhibited a more potent photocytotoxic effect than HP and largely addressed the inconvenience issue associated with the use of HP. Thereby, hypericin may be a better alternative to HP in treating PWSs.