Photodynamically induced effects in colon carcinoma cells (WiDr) by endogenous photosensitizers generated by incubation with 5-aminolaevulinic acid

J Photochem Photobiol B. 1999 Apr;49(2-3):162-70. doi: 10.1016/s1011-1344(99)00051-2.

Abstract

Human adenocarcinoma cells of the line WiDr have been treated with 2 mM 5-aminolaevulinic acid (5-ALA) in the presence of 10% foetal calf serum. The treatment induces a linear accumulation of protoporphyrin IX (PpIX) for at least 7.5 h. After 7.5 h of incubation about 45% of the PpIX accumulated is cell-bound, while the rest is found in the medium (25%) or lost from the cells during washing with phosphate-buffered saline (30%). Exposure to white light at an intensity of 30 W/m2 for 18 min results in 95% reduction of clonogenicity in cells treated with 2 mM 5-ALA for 3.5 h. The enzymatic activities of enzymes located in cytosol (glyceraldehyde 3-phosphate dehydrogenase and lactate dehydrogenase) and lysosomes (acid phosphatase and beta-glucuronidase) are not influenced by a 5-ALA and light treatment inactivating about 35% of the cells. The MTT assay, which reflects mitochondrial dehydrogenase activity, but not succinate dehydrogenase, is partly inhibited by the same treatment. Treatment with 5-ALA in the absence of light increases O2 consumption by a factor of two, while the O2 consumption is inhibited when 5-ALA treatment is combined with exposure to light. In addition, 5-ALA and light exposure enhance accumulation of rhodamine 123 by 40% and reduce the intracellular ATP level by 25%. Confocal laser scanning microscopical analysis indicates granular perinuclear localization of the PpIX formed by 5-ALA treatment. In conclusion, photodynamic treatment using 5-ALA as a prodrug induces damage to mitochondrial function without inhibiting lysosomal and cytosolic marker enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Aminolevulinic Acid / therapeutic use*
  • Biomarkers, Tumor
  • Colonic Neoplasms / drug therapy*
  • Fluorescent Dyes / pharmacokinetics
  • Heptanoates / pharmacology
  • Humans
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Oxygen Consumption / drug effects
  • Photochemotherapy
  • Photosensitizing Agents / therapeutic use*
  • Protoporphyrins / metabolism
  • Rhodamine 123 / pharmacokinetics
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Fluorescent Dyes
  • Heptanoates
  • Photosensitizing Agents
  • Protoporphyrins
  • Rhodamine 123
  • succinylacetone
  • Aminolevulinic Acid
  • Adenosine Triphosphate
  • protoporphyrin IX