Singlet Oxygen, Photodynamic Therapy, and Mechanisms of Cancer Cell Death

Figure 7

Extrinsic and intrinsic apoptotic pathways. (a) Oxidative stress induced due to photodynamic therapy (PDT) causes the activation of the Fas receptor, which binds with FADD followed by procaspase-8 to form a complex. This complex is called a death-inducing signaling complex (DISC), and it cleaves procaspase-8 into caspase-8. Caspase-8 cleaves caspase-3 and caspase-7. Caspase-3 releases caspase-activated deoxyribonuclease (CAD) from inhibitor of caspase-activated DNase (ICAD), which induces DNA fragmentation, whereas caspase-7 degrades the cellular proteins. (b) The activity of photosensitizer has been shown to contribute to the inhibition of Bcl-2 protein and increase in expression of BAX proteins. BAX increases mitochondrial outer membrane permeability, which causes the mitochondria to release cytochrome c into the cytoplasm. In the cytoplasm, cytochrome c binds with APAF1 and procaspase-9 to form apoptosomes. Apoptosome is responsible for the cleavage of caspase-9, which leads to the activation of caspase-3. Caspase-3 induces apoptosis via DNA fragmentation and cellular protein degradation.

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