Signaling pathways involved in the regulation of apoptosis following photodynamic therapy

Hypericin, a photosensitizer synthesized by Hypericum perforatum plants, holds promise as anticancer tool in Photodynamic therapy (PDT). PDT with hypericin can cause G2/M arrest, apoptosis or necrosis in a concentration- and light-dose-dependent fashion. Apoptosis is mediated by the mitochondrial pathway of caspase activation and is delayed by the ovcrexpression of Bcl-2. At lower doses, PDT with hypericin induces a G2/M arrest that precedes apoptosis and is associated with the phosphorylation of mitochondrial Bcl-2. This Bcl-2 phosphorylation requires the activation of the cyclin-dependent protein kinase1 (CDK1) and appears to be a mechanism to delay the onset of apoptosis in mildly photodamaged cells. Hence, PDT with hypericin results in the activation of multiple pathways that can either promote or restrain apoptosis.