title: Subcellular localization pattern of protoporphyrin IX is an important determinant for its photodynamic efficiency of human carcinoma and normal cell lines.
abstract: Photodynamic therapy (PDT) is a combination of light with a lesion-localizing photosensitizer or its precursor to destroy the lesion tissue. PDT has recently become an established modality for several malignant and non-malignant conditions, but it can be further improved through a better understanding of the determinants affecting its therapeutic efficiency. In the present investigation, protoporphyrin IX (PpIX), an efficient photosensitizer either endogenously induced by 5-aminolevulinic acid (ALA) or exogenously administered, was used to correlate its subcellular localization pattern with photodynamic efficiency of human oesophageal carcinoma (KYSE-450, KYSE-70) and normal (Het-1A) cell lines. By means of fluorescence microscopy ALA-induced PpIX was initially localized in the mitochondria, whereas exogenous PpIX was mainly distributed in cell membranes. At a similar amount of cellular PpIX PDT with ALA was significantly more efficient than photodynamic treatment with exogenous PpIX at killing all the 3 cell lines. Measurements of mitochondrial membrane potential and intracellular ATP content, and electron microscopy showed that the mitochondria were initially targeted by ALA-PDT, consistent with intracellular localization pattern of ALA-induced endogenous PpIX. This indicates that subcellular localization pattern of PpIX is an important determinant for its PDT efficiency in the 3 cell lines. Our finding suggests that future new photosensitizers with mitochondrially localizing properties may be designed for effective PDT.
authors.affiliation: Department of Pathology, The National Hospital-Norwegian Radium Hospital, University of Oslo, Montebello, 0310 Oslo, Norway.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ji
authors.forename: Guanrui
authors.initials: G
authors.lastname: Yang
authors.forename: Vlada
authors.initials: V
authors.lastname: Vasovic
authors.forename: Beata
authors.initials: B
authors.lastname: Cunderlikova
authors.forename: Zhenhe
authors.initials: Z
authors.lastname: Suo
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.forename: Qian
authors.initials: Q
authors.lastname: Peng
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000648:ultrastructure; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000378:metabolism / Q000494:pharmacology; D011524:Protoporphyrins / Q000378:metabolism* / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; D000255:Adenosine Triphosphate; C028025:protoporphyrin IX