title: Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro.
abstract: BACKGROUND
  Meso-tetra-hydroxyphenyl-chlorine (mTHPC) is among the most powerful photosensitizers available for photodynamic therapy (PDT). However, the mechanisms leading to cell death are poorly understood. We here focused on changes at DNA and RNA levels after treatment with the liposomal mTHPC derivative Foslipos in vitro.
  
  
  METHODS
  After determination of darktoxicity, laser conditions and uptake kinetics, PC-3 prostate carcinoma cells were subjected to PDT with Foslipos, followed by assessment of cell numbers directly (TP0) or 1h (TP1), 2h (TP2), 5h (TP5) and 24h (TP24) after illumination. Nucleic acids had been extracted for evaluation of RNA amounts and integrity as well as for estimation of abasic sites as a measure for DNA damage. Furthermore, expression changes of 84 genes related to oxidative stress were investigated by quantitative polymerase chain reaction.
  
  
  RESULTS
  Already at TP0, the number of dead cells was significantly higher after PDT versus controls and at TP24 more than 90% of cells had been destroyed. PDT resulted in a severe damage of both RNA and DNA. Gene expression analyses revealed an impact of PDT on pathways for oxidative and metabolic stress, heat shock, proliferation and carcinogenesis, growth arrest, inflammation, DNA repair and apoptosis signaling.
  
  
  CONCLUSIONS
  Mechanisms of Foslipos-mediated PDT comprise a combination of acute and delayed lethal effects in PC-3 cells. The latter may include death processes initiated by nucleic acid damage, activation of stress and growth arrest genes in combination with a reduced capability to adequately cope with oxidative toxicity. Our results will help to better understand molecular photodynamic effects.
authors.affiliation: Institute of Anatomy, University of Zurich, Switzerland.
authors.forename: Emina Besic
authors.initials: EB
authors.lastname: Gyenge
authors.forename: Seraina
authors.initials: S
authors.lastname: Hiestand
authors.forename: Susanna
authors.initials: S
authors.lastname: Graefe
authors.forename: Heinrich
authors.initials: H
authors.lastname: Walt
authors.forename: Caroline
authors.initials: C
authors.lastname: Maake
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008081:Liposomes; D008297:Male; D008652:Mesoporphyrins / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012334:RNA, Neoplasm / Q000187:drug effects
chemical_list: D004273:DNA, Neoplasm; D008081:Liposomes; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D012334:RNA, Neoplasm; C072269:temoporfin