title: In vitro and in vivo antitumor activity of a novel hypocrellin B derivative for photodynamic therapy.
abstract: BACKGROUND
  Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts cytotoxic activity toward tumor cells by irradiating photosensitizers with light exposure to produce reactive oxygen species (ROS). An ideal photosensitizer is a crucial element to PDT. In the current study, we evaluated the photodynamic activity of a novel photosensitizer, the derivative of hypocrellin B (HB), 17-(3-amino-1-pentanesulfonic acid)-substituted hypocrellin B Schiff-base (PENSHB), both in vitro and in vivo.
  
  
  METHODS
  Physicochemical characteristics of the novel photosensitizer were compared with that of its parent HB. The intracellular distribution of photosensitizers and mitochondrial membrane potential were detected with laser scanning confocal microscopy. The pathway of cell death was analyzed by flow cytometry. The release of proapoptotic proteins was evaluated by Western blot. S180 tumor model was used to evaluate the antitumor effects of PENHB-mediated PDT.
  
  
  RESULTS
  Compared with its parent HB, water solubility of the derivative was improved enormously (6.6 mg/ml vs. 4.6 μg/ml), rendering its intravenous injection feasible without auxiliary solvent. The derivative had better PDT effect than HB in vitro under similar dark cytotoxicity. Moreover, PENSHB-mediated PDT was able to induce mitochondrial inner membrane permeabilisation, cytochrome c release, caspase-3 activation and subsequent apoptotic death. In vivo study showed that more than half of tumor bearing mice were cured by PENSHB-mediated PDT.
  
  
  CONCLUSIONS
  In vitro and in vivo studies suggest that PENSHB is an effective photosensitizer for PDT to tumors. Therefore, PENSHB as a novel photosensitizer has a good prospect of clinical application.
authors.affiliation: Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Hongyou
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Dermatology, The Second Hospital, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yin
authors.affiliation: School of Information and Electronics, Beijing Institute of Technology, Beijing 100081, PR China.
authors.forename: Defu
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: College of Medicine, Nankai University, Tianjin 300071, PR China.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Zhanga
authors.affiliation: Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Naiyan
authors.initials: N
authors.lastname: Huang
authors.affiliation: Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Qianli
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, PR China.
authors.forename: Jingquan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China. Electronic address: guyinglaser301@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D010569:Perylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011809:Quinones / Q000138:chemical synthesis* / Q000627:therapeutic use*; D012545:Schiff Bases / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011809:Quinones; D012545:Schiff Bases; D010569:Perylene; C064522:hypocrellin B
keywords: Apoptosis; Hypocrellin B derivative; In vivo PDT activity; Mitochondria; PDT