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Background: Photodynamic Therapy (PDT) is a promising antitumor and anti-bacterial treatment method for its high selectivity, non-invasiveness, and minimal side effects. However, cellular mechanisms may lead to PDT resistance and thus effect efficacy. The aim of this study is to test whether Curcumin, which is a non-toxic natural compound that has antitumor characteristics, can increase PDT efficacy by overcoming the resistance of cancer cells., Methods: 5-ALA mediated PDT was tested on two cell lines, PC-3 and Caco-2. Curcumin toxicity was evaluated at different concentrations. The determined PDT doses were applied to the cell lines together with two different Curcumin concentrations. Cell viability was evaluated by MTT assay, 24 hs after the treatments. Results were evaluated using One-Way ANOVA followed by post-hoc tests., Results: Using non-toxic doses of Curcumin resulted in a significant decrease in PDT resistance in Caco-2 cells and thus increased the efficacy of 5-ALA mediated PDT, but not on PC-3. Adding Curcumin to 5-ALA mediated PDT led to more effective results on Caco-2 with a 62.4% decrease in cell viability. On the other hand, adding Curcumin to 5-ALA mediated PDT on PC-3 cells didn't produce statistically significant increase in efficacy with a 36% decrease in cell viability., Conclusion: 5-ALA mediated PDT combined with Curcumin synergistically enhanced antitumor PDT efficacy on Caco-2, which is considered a highly resistive cancer cell line., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The Food and Drug Administration-approved Indocyanine Green can be used as a photosensitizer to kill cancer cells selectively. Although indocyanine green is advantageous as a photosensitizer in terms of strong absorption in the near-infrared region, indocyanine green-based cancer treatment is still not approved as a clinical method. Some reasons for this are aggregation at high concentrations, rapid clearance of the photosensitizer from the body, low singlet oxygen quantum yield, and the uncertainty concerning its action mechanism. This in vitro study focuses on two of these points: "what is the cell inhibition mechanism of indocyanine green-based therapy?" and "how the dose-dependent aggregation problem of indocyanine green alters its cell inhibition efficiency?" The following experiments were conducted to provide insight into these points. Nontoxic doses of indocyanine green and near-infrared laser were determined. The aggregation behavior of indocyanine green was verified through experiments. The singlet oxygen quantum yield of indocyanine green at different concentrations were calculated. Various indocyanine green and energy densities of near-infrared light were applied to prostate cancer, neuroblastoma, and colon cancer cells. An MTT assay was performed at the end of the first, second, and third days following the treatments to determine the cell viability. Temperature changes in the medium during laser exposure were recorded. ROS generation following the treatment was verified by using a Total Reactive Oxygen Species detection kit. An apoptosis detection test was performed to establish the cell death mechanism and, finally, the cellular uptakes of the three different cells were measured. According to the results, indocyanine green-based therapy causes cell viability decrease for three cancer cell lines by means of excessive reactive oxygen species production. Different cells have different sensitivities to the therapy possibly because of the differentiation level and structural differences. The singlet oxygen generation of indocyanine green decreases at high concentrations because of aggregation. Nevertheless, better cancer cell killing effect was observed at higher photosensitizer concentrations. This result reveals that the cellular uptake of indocyanine green was determinant for better cancer cell inhibition., (Copyright © 2018 Elsevier B.V. All rights reserved.)