Effects of 5-aminolaevulinic acid on human ovarian cancer cells and human vascular endothelial cells in vitro.
Results are reported on the cellular effects and the sensitivity of cultured tumor epithelial cells (TEC) derived from human ovarian cystadenocarcinoma and human umbilical vein-derived endothelial cells (HUVEC) to exogenous 5-aminolaevulinic acid (ALA) and ALA-induced photodynamic therapy (PDT). Cellular alterations and PDT efficiency were evaluated using colorimetric thiazolyl blue (MTT) assay, trypan blue exclusion assay, electron microscopy, and gel electrophoresis. ALA-induced protoporphyrin IX (PpIX) accumulation in TEC was associated with a concentration and time-dependent significant decrease in mitochondrial activity, increase in cell membrane permeability, and dark toxicity. Maximum PpIX loaded TEC demonstrated a high sensitivity to PDT. Neither cellular alterations nor PDT effects were observed in HUVEC under identical experimental conditions. These results indicate a potential clinical value for the use of ALA-mediated PDT to treat minimal residual disease in mucinous ovarian carcinoma. In addition, the ALA-induced PpIX cytotoxicity may be exported to a new chemotherapeutic regimen via a conventionally viewed photochemotherapeutic agent.
Spörri
S
S
Department of Obstetrics and Gynecology, University of Bern, 3012, Bern, Switzerland. sspoerri@bluewin.ch
Chopra
V
V
Egger
N
N
Hawkins
H K
HK
Motamedi
M
M
Dreher
E
E
Schneider
H
H
D000622:Aminolevulinic Acid / Q000493:pharmacokinetics / Q000633:toxicity*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018282:Cystadenocarcinoma, Mucinous / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007700:Kinetics; D008027:Light; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000473:pathology*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D011524:Protoporphyrins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX