Glucose is Required to Maintain High ATP-levels for the Energy-utilizing Steps During PDT-induced Apoptosis

Photodynamic therapy (PDT) may trigger apoptosis or necrosis in cancer cells. Several steps in the induction and execution of apoptosis require high amounts of adenosine-5′-triphosphate (ATP). Because the mitochondrial membrane potential (Δψ) decreases early in apoptosis, we raised the question about the mechanisms of maintaining a sufficiently high ATP level. We therefore monitored Δψ and the intracellular ATP level of apoptotic human epidermoid carcinoma cells (A431) after photodynamic treatment with aluminum (III) phthalocyanine tetrasulfonate. A maximum of caspase-3–like activity and nuclear fragmentation was found at fluences of about 4 J cm–2. Under these conditions apoptotic cells reduced Δψ rapidly, while the ATP level remained high for 4–6 h after treatment for cells supplied with glucose. To analyze the contribution of glycolysis to the energy supply during apoptosis, experiments were carried out with cells deprived of glucose. These cells showed a rapid drop of ATP content and neither caspase activation nor nuclear fragmentation could be detected. We conclude that the use of glucose as a source of ATP is obligatory for the execution of PDT-induced apoptosis.