title: Hypericin-photodynamic therapy induces human umbilical vein endothelial cell apoptosis.
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.
authors.affiliation: Department of Pharmacy, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors.forename: Zhuo-heng
authors.initials: ZH
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors.forename: San-jun
authors.initials: SJ
authors.lastname: Shi
authors.affiliation: Office of Clinical Pharmacological Center, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, P. R. China.
authors.forename: Shi-wen
authors.initials: SW
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Fu
authors.affiliation: Department of Pharmacy, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors.forename: Ruo-qiu
authors.initials: RQ
authors.lastname: Fu
authors.affiliation: Department of Pharmacy, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China.
authors.forename: Lai-chun
authors.initials: LC
authors.lastname: Lu
mesh_terms: D000873:Anthracenes; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D008027:Light; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000873:Anthracenes; D053148:Caspase 3; D016207:Cytokines; D010569:Perylene; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; C004965:hypericin