Photodynamic therapy (
PDT) can result in both types of cell death, apoptosis or
necrosis. Several steps in the induction and execution of apoptosis depend on
ATP and the intracellular
ATP level has been shown to be one determinant in whether apoptosis or
necrosis occurs. Therefore, photochemical damage of cellular targets involved in energy supply might play a crucial role in the mode of cell death being executed. The present study is aimed at the characterization of changes in cellular energy supply and the associated cell death modes in response to
PDT. Using the human
epidermoid carcinoma cell line A431 and
aluminium(III)
phthalocyanine tetrasulfonate chloride (2.5 microM) as a
photosensitizer, we studied the changes in mitochondrial function and intracellular
ATP level after irradiation with different light doses. Employing assays for
caspase-3 activation and nuclear fragmentation, 50% of the cells were found to undergo apoptosis after irradiation between 2.5 to 3.5 J cm(-2) while the remainder died by
necrosis. At higher light doses (> 6 J cm(-2)), neither
caspase-3 activation nor nuclear fragmentation was observed and this suggests that these cells died exclusively by
necrosis. Necrotic cell death was also associated with a rapid decline in mitochondrial activity and intracellular
ATP. By contrast, with apoptosis the loss of mitochondrial function was delayed and the
ATP level was maintained at near control levels for up to eight hours which was far beyond the onset of morphological changes. These data suggest that, depending on the light dose applied, both,
necrosis as well as apoptosis can be induced with
AlPcS4 mediated
PDT and that photodamage in energy supplying cellular targets may influence the mode of cell death. Further, it is speculated that cells undergoing apoptosis in response to
PDT might maintain a high
ATP level long enough to complete the apoptotic program.