Combination treatment with photodynamic therapy and curcumin induces             mitochondria-dependent apoptosis in AMC-HN3 cells.
Photodynamic therapy (PDT) is a treatment for the selective destruction             of cancerous and non-neoplastic cells that involves the simultaneous presence             of light, oxygen and a light-activatable chemical known as a photosensitizer.             Curcumin is one of the most extensively investigated phytochemicals with chemopreventive             potential and antitumor effects. In this study, the effect of a combination of             PDT and curcumin on apoptotic cell death in AMC-HN3 cells and the molecular mechanism             underlying apoptosis was examined to confirm the interaction between photofrin-induced             PDT and curcumin during combined mortality. The combination treatment with curcumin             and PDT inhibited approximately 70% of the cell viability after PDT, whereas the             PDT and curcumin only groups showed a 50 and 10% decrease in cell viability, respectively.             In addition, the combination treatment increased the apoptotic events, such as             nuclear fragmentation and nuclear condensation. This combination group showed             an increase in ROS generation that was higher than that observed after each single             treatment. Compared to the single agent treatments, the combination therapy induced             the enhanced loss of ∆ψm. Furthermore, the cytosolic levels of cytochrome c were             significantly elevated in the combination group. Caspases-9, -3 and PARP, which             are apoptosis-related proteins induced by mitochondrial activation, were upregulated             remarkably by the combination treatment. When co-treated with glutathione, a singlet             oxygen quencher, the combination treatment-induced synergistic cytotoxic and apoptotic             effects, enhanced the generation of ROS and suppressed the upregulation of caspase-3             and PARP. These results suggest that the combination modality with PDT and curcumin             have a better treatment effect in vitro. The induction of mitochondrial-dependent             apoptosis due to the increased generation of ROS may be involved in this combination             treatment.
Medical Laser and Device Research Center, Dankook University,                     Cheonan 330-714, Republic of Korea.
Jin-Chul
JC
Ahn
Jung-Wook
JW
Kang
Jang-In
JI
Shin
Phil-Sang
PS
Chung
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology* / Q000633:toxicity; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000633:toxicity; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9; D005978:Glutathione; D003474:Curcumin