Delta-aminolevulinic acid-mediated photosensitization of prostate cell lines: implication for photodynamic therapy of prostate cancer.
BACKGROUND
Delta-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) is currently being investigated for the treatment of prostate diseases. In this study, we evaluate 1) the in vitro production of protoporphyrin IX (PPIX) (the active photosensitizing agent of ALA-mediated PDT) by two different prostate cancer cell lines (LNCaP and PC-3) and a benign, modified, prostatic cell line (TP-2), and 2) the extent of PDT-induced cell injury, as determined by electron microscopy (EM) and cell survival.


METHODS
The cell lines were assigned into four treatment groups: group 1, control, no ALA and no light irradiation; group 2, dark control, ALA only; group 3, light control, radiation only; and group 4, PDT, ALA followed by irradiation (630 nm, 3 joules/cm2). The experiments were performed in triplicate. ALA concentration was 50 microg/ml of media in all instances.


RESULTS
Following incubation with ALA, PPIX production was significantly increased in the three cell lines studied, and more notably in the PC-3 cell line. Compared to controls, EM and cell survival studies demonstrated significant mitochondrial damage and decreased survival, respectively, in the cells treated with PDT. This was also more evident in the PC-3 cell line.


CONCLUSIONS
Our results demonstrate that prostate cells differ in their response to ALA-mediated PDT. This response appears to depend on the intracellular production of PPIX and the cell type, i.e., on the functional and structural characteristics of the cell mitochondria. In addition, our results suggest that PDT might be effective at killing prostate cancer cells.
Department of Surgery, University of Texas Medical Branch, Galveston 77555, USA.
P
P
Chakrabarti
E
E
Orihuela
N
N
Egger
D E
DE
Neal
R
R
Gangula
A
A
Adesokun
M
M
Motamedi
D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure; D011524:Protoporphyrins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX