Hedyotis corymbosa (L.) LAMARCK (Rubiaceae) has been used in traditional Chinese medicine and found to have anti-tumor effect. The major purpose of this study was to characterize the effects and mechanisms of apoptosis induced by photodynamic therapy (PDT) with Hedyotis corymbosa extracts in M21 skin cancer cells. PDT was found to be an effective therapy for local malignant tumors. Our study indicated by 0.8 J/cm2 fluence dose caused cells death. PDT with H. corymbosa extracts-induced M21 cells death is a typical apoptosis that was accompanied by formation of apoptotic bodies, nuclear condensation and externalization of phosphatidylserine. In this study, PDT with H. corymbosa extracts-induced apoptosis of M21 cells involved modulation of the expression of apoptosis-related proteins, such as Bcl-2 and caspase family members, and mitochondrial function, such as opening mitochondrial permeability transition pore, disruption of mitochondrial membrane potential and the decrease in mitochondria uptake activity. We also demonstrated that cytoskeleton is the target of PDT with H. corymbosa extracts-induced M21 cells apoptosis. The change of distribution of F-actin was partly inhibited by pretreatment with phalloidin, an actin-stabilizing agent. PDT with H. corymbosa extracts-induced the disruption of mitochondrial membrane potential was also partly blocked by pretreatment with phalloidin. It seems to indicate that cytoskeleton lies upstream of mitochondria in PDT with H. corymbosa extracts-induced M21 cells apoptosis. Furthermore, we have demonstrated that the endoplasmic reticulum stress was involved in H. corymbosa extracts-induced apoptosis in M21 skin cancer cells.
