Combination treatment with photodynamic therapy and curcumin induces mitochondria-dependent apoptosis in AMC-HN3 cells

Abstract

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.

Curcumin Inhibits MHCC97H Liver Cancer Cells by Activating ROS/TLR-4/Caspase Signaling Pathway

“…It was reported that curcumin suppressed the expression of cyclin D1 to limit cell progression in cell cycle (Mukhopadhyay et al, 2002). Curcumin also could activate mitochondriadependent apoptotic signaling pathway, leading to up-regulation of caspase cascade in tumor cell (Ahn et al, 2012). Curcumin's role of suppressing activation of NF-κB regulated antiapoptotic genes was also testified by previous study (Shakibaei et al, 2013).…”

Effects of combination of melatonin and laser irradiation on ovarian cancer cells and endothelial lineage viability

“…Despite the apparent benefits generated by the application of PDT and chemotherapy treatments alone, these methods have disadvantages such as high burden of toxicity for the assurance of tumor regression. Therefore, the combination of PDT along with an apoptotic agent not only boosts the efficacy of the treatment but also can decrease the doses of chemotherapy drugs and thereby unwanted side effects [9,11]. Several studies have been shown that the concurrent combination of PDT with different chemotherapeutic agents can generally enhance the efficacy of chemotherapeutics in induction of apoptosis [9,11,13].…”

“…Because of low toxicity and high selectively rate, a deal of attention has recently been concentrated mostly on the application of PDT in the field of tumor biology [10,11]. To achieve profound efficiency pertaining to PDT, the necessity of modalities such as simultaneous presence of light, oxygen, and appropriate photosensitizer should be considered [12].…”

Curcumin induces the apoptosis of A549 cells via oxidative stress and MAPK signaling pathways

“…Additionally, previous studies have shown that curcumin exhibits antiproliferative and anticarcinogenic properties in a wide variety of cell lines and animals (10,11). Previous studies have demonstrated that curcumin inhibits the growth and apoptosis of human A549 lung adenocarcinoma cells (12)(13)(14).…”