Analysis of mitochondrial activity related to cell death after PDT with AlPCS(4).
OBJECTIVE
The aim of this study was to report that photodynamic therapy (PDT) with mitochondria-associated chloroaluminum phthalocyanine tetrasulfonate (AlPcS(4)) leads to significant alterations in this organelle.


BACKGROUND
PDT is a viable treatment modality for a variety of tumors, as well as for some non-oncologic diseases. The procedure submits cells or tissue to a photosensitizing drug followed by light irradiation of appropriate wavelength, usually in the red area or close to infrared, and compatible with the drug absorption spectrum, inducing the apoptotic process. However, the precise mechanism of PDT-induced apoptosis is not well characterized. Several cellular organelles can be postulated as the target for PDT with different photosensitizers such as plasmatic membrane, nucleus, mitochondria, endoplasmic reticulum, Golgi complex, and others. The mitochondrion is the main target in PDT because it is the main organelle involved in apoptosis. One of the main agents is cytochrome c, a proapoptotic factor that preferentially links itself to the mitochondrial cardiolipin.


METHODS
The photosensitizing effects of AlPcS(4) were studied in the mitochondria. Cells were irradiated with a diode laser (670 nm, energy density of 4.5 J/cm(2), and power density of 45 mW/cm(2)).


RESULTS
The fluorescent analyses of the mitochondria were performed with MitoTracker and nonyl acridine orange (NAO), and electron microscopy demonstrated that PDT with AlPcS(4) leads to significant alterations in mitochondria, causing membrane potential loss, alteration in cardiolipin distribution and cell death.


CONCLUSIONS
The labels with Mitotracker and NAO demonstrated mitochondrial migration to the perinuclear region, confirmed through electron microscopy, suggesting that intact mitochondria were solicited for possible DNA fragmentation.
Tamietti
B F Perrin
BF
Laboratório de Dinâmica de Compartimentos Celulares, Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, São José dos Campos, S.P., Brazil.
Machado
A H A
AH
Maftoum-Costa
M
M
Da Silva
N S
NS
Tedesco
A C
AC
Pacheco-Soares
C
C
D000165:Acridine Orange / Q000031:analogs & derivatives; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004396:Coloring Agents; D053938:DNA Fragmentation; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000528:radiation effects / Q000648:ultrastructure; D009942:Organometallic Compounds / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology
D004396:Coloring Agents; D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C052736:chloroaluminum tetrasulfophthalocyanine; C056258:N(10)-nonylacridine orange; D000165:Acridine Orange