title: Comparison between endothelial and tumor cells in the response to verteporfin-photodynamic therapy and a PI3K pathway inhibitor.
abstract: BACKGROUND
  Photodynamic therapy (PDT) is an established cancer treatment. Molecular-targeted agents targeting phosphatidylinositol 3-kinase (PI3K) pathway is showing great promise as anticancer drugs. This study compared SVEC mouse endothelial and PC-3 human prostate tumor cells in the response to verteporfin-mediated photodynamic therapy (PDT) and a pan-PI3K pathway inhibitor LY294002.
  
  
  METHODS
  Verteporfin cellular uptake and intracellular localization was determined by spectrofluorometry and confocal fluorescence microscopy, respectively, in the SVEC and PC-3 cells. Cytotoxicity induced by LY294002 and verteporfin-PDT was assessed by the MTS assay. Effects of treatments on cell survival and death signaling were examined by Western blot analysis.
  
  
  RESULTS
  PC-3 cells had a higher cellular uptake of verteporfin than SVEC cells at 15min after incubation with verteporfin. Verteporfin was mainly localized in mitochondria in both SVEC and PC-3 cells. Verteporfin-PDT alone as well as PDT in combination with LY294002 induced more apoptosis and caused more reduction in cell viability in SVEC cells than in PC-3 cells. PC-3 cells exhibited a higher level of anti-apoptotic Bcl-2 family proteins than SVEC cells.
  
  
  CONCLUSIONS
  SVEC cells were more responsive to verteporfin-PDT and PI3K pathway inhibitor LY294002 than PC-3 cells. Such differences in response were likely due to differences in Bcl-2 family protein level. These results support tumor vascular targeting by verteporfin-PDT and its therapeutic enhancement by PI3K pathway inhibition.
authors: Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA 19104, USA.
authors: Babasola
authors: B
authors: Fateye
authors: Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA 19104, USA.
authors: Aaron
authors: A
authors: Wan
authors: Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA 19104, USA.
authors: Xue
authors: X
authors: Yang
authors: Department of Biological Sciences, Misher College of Arts & Sciences, University of the Sciences, Philadelphia, PA 19104, USA.
authors: Kenneth
authors: K
authors: Myers
authors: Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA 19104, USA. Electronic address: b.chen@usciences.edu.
authors: Bin
authors: B
authors: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002867:Chromones / Q000627:therapeutic use; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009025:Morpholines / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011166:Porphyrins / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D000077362:Verteporfin
chemical_list: D000970:Antineoplastic Agents; D002867:Chromones; D009025:Morpholines; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases
keywords: Apoptosis; LY294002; Phosphatidylinositol 3-kinase (PI3K) inhibitor; Photodynamic therapy (PDT); Verteporfin