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Hypericin-photodynamic therapy induces human umbilical vein endothelial cell apoptosis
Qian Zhang, Zhuo-heng Li, Yuan-yuan Li, San-jun Shi, Shi-wen Zhou, Yuan-yuan Fu, Qing Zhang, Xue Yang, Ruo-qiu Fu & Lai-chun Lu
Abstract
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.
Hypericin (HY) was purchased from Chengdu Biopurify Phytochemicals (batch no. 081204, purity 99.1%, Chengdu, China).