Hypericin-photodynamic therapy induces human umbilical vein endothelial cell apoptosis.

Qian Zhang,Shi-Wen Zhou,Xue Yang,Lai-Chun Lu,San-Jun Shi,Qing Zhang,Yuan-Yuan Li,Yuan-Yuan Fu,Ruo-Qiu Fu,Zhuo-Heng Li

doi:10.1038/srep18398

Qian Zhang, Shi-Wen Zhou + Show 8 more

Open Access

https://doi.org/10.1038/srep18398

Copy DOI

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.

Highlights

The inconvenience issue associated with the use of other photosensitizers
We found that hypericin induced apoptosis in human umbilical vein endothelial cells (HUVECs)
We discovered that hypericin induced apoptosis via Bax/Bcl-2 ratio upregulation, Δ Ψ m collapse, accompanied with cyto c release, procaspase-3, procaspase-9 and PARP cleavage, and VEGF-A suppression, p-Akt inhibition and Bad dephosphorylation

Summary

Introduction

The great potential of hypericin as an excellent alternative photosensitizer prompted us to further explore its reaction mechanism. Human umbilical vein endothelial cells (HUVECs) were used as the model to investigate how hypericin induces photocytotoxicity. We found that hypericin induced apoptosis in HUVECs. we evaluated the effects of hypericin on the mitochondrial apoptotic pathway and the VEGF-A-mediated PI3K/ Akt pathway. We discovered that hypericin induced apoptosis via Bax/Bcl-2 ratio upregulation, Δ Ψ m collapse, accompanied with cyto c release, procaspase-3, procaspase-9 and PARP cleavage, and VEGF-A suppression, p-Akt inhibition and Bad dephosphorylation. Hypericin exhibited a more potent photocytotoxic effect on the above-mentioned pathways than haematoporphyrin.

Methods

Results

Conclusion