Photodynamic effects induced by aminolevulinic acid esters on human cervical carcinoma cells in culture.
Fluorescence diagnosis and photodynamic therapy using 5-aminolevulinic acid (ALA) provide new methods for the detection and treatment of cervical cancer and especially its precursors. However, these techniques are restricted by the rate of uptake of the hydrophilic ALA, its poor diffusion through the bilayer of biological membranes or both. In this study we evaluated the effect of some esterified ALA derivatives on the induction of the endogenous photosensitizer, protoporphyrin IX (PpIX), and the photodamage in cultured human cervical cells (C33-A and CaSki). The kinetics of PpIX accumulation showed that ALA esters, especially the ALA-hexylester (h-ALA), induced significantly faster PpIX formation than ALA at the same concentration (0.5 mM). The PpIX induction showed a dose-dependent characteristic. The highest PpIX values could be achieved by an up to 1.3-13-fold lower concentration of ALA esters than with ALA. Using the Annexin V assay, apoptosis was found to be induced rapidly after irradiation in both ALA- and ALA esters-treated cells. On measuring mitochondrial activity, the incubation with h-ALA induced a more pronounced photodamage. The results indicate that improved or at least comparable photodynamic effects can be achieved by using remarkably lower doses of ALA esters.
Xiang
W
W
Department of Obstetrics and Gynecology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
Weingandt
H
H
Liessmann
F
F
Klein
S
S
Stepp
H
H
Baumgartner
R
R
Hillemanns
P
P
D000622:Aminolevulinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000188:drug therapy / Q000628:therapy; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004952:Esters / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000201:enzymology; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011524:Protoporphyrins / Q000378:metabolism; D013052:Spectrometry, X-Ray Emission; D014407:Tumor Cells, Cultured / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000628:therapy
D017304:Annexin A5; D004952:Esters; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX