scholarly journals Metalloporphyrin Pd(T4) Exhibits Oncolytic Activity and Cumulative Effects with 5-ALA Photodynamic Treatment against C918 Cells

2020 ◽  
Vol 21 (2) ◽  
pp. 669
Author(s):  
Brandon Leviskas ◽  
Tibor Valyi-Nagy ◽  
Gnanasekar Munirathinam ◽  
Matthew Bork ◽  
Klara Valyi-Nagy ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Photodynamic Therapy ◽  
Aminolevulinic Acid ◽  
Vasculogenic Mimicry ◽  
Three Dimensional ◽  
Reactive Oxygen ◽  
Cumulative Effects ◽  
Oxygen Species ◽  
Illumination Time

Photodynamic therapy is a non-invasive method where light activates a photosensitizer bound to cancer cells, generating reactive oxygen species and resulting in cell death. This study assessed the oncolytic potential of photodynamic therapy, comparing European Medicines Agency and United States Food and Drug Administration-approved 5-aminolevulinic acid (5-ALA) to a metalloporphyrin, Pd(T4), against a highly invasive uveal melanoma cell line (C918) in two- and three-dimensional models in vitro. Epithelial monolayer studies displayed strong oncolytic effects (>70%) when utilizing Pd(T4) at a fraction of the concentration, and reduced pre-illumination time compared to 5-ALA post-405 nm irradiance. When analyzed at sub-optimal concentrations, application of Pd(T4) and 5-ALA with 405 nm displayed cumulative effects. Lethality from Pd(T4)-photodynamic therapy was maintained within a three-dimensional model, including the more resilient vasculogenic mimicry-forming cells, though at lower rates. At high concentrations, modality of cell death exhibited necrosis partially dependent on reactive oxygen species. However, sub-optimal concentrations of photosensitizer exhibited an apoptotic protein expression profile characterized by increased Bax/Bcl-2 ratio and endoplasmic stress-related proteins, along with downregulation of apoptotic inhibitors CIAP-1 and -2. Together, our results indicate Pd(T4) as a strong photosensitizer alone and in combination with 5-ALA against C918 cells.

Synthesis and evaluation of new 5-aminolevulinic acid derivatives as prodrugs of protoporphyrin for photodynamic therapy

2017 ◽  
Vol 16 (11) ◽  
pp. 1623-1630 ◽  
Author(s):  
Wei Zhu ◽  
Ying-Hua Gao ◽  
Chun-Hong Song ◽  
Zhi-Bin Lu ◽  
Tabbisa Namulinda ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Aminolevulinic Acid ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Light Activation ◽  
S180 Cell

Upon light activation, 13a can induce the production of PpIX in vivo which produces ROS and other reactive oxygen species to lead to the apoptosis of S180 cell tumors.

scholarly journals Combination of photodynamic therapy (PDT) and anti-tumor immunity in cancer therapy

2018 ◽  
Vol 48 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Hee Sook Hwang ◽  
Heejun Shin ◽  
Jieun Han ◽  
Kun Na
Keyword(s):  
Reactive Oxygen Species ◽  
Immune Response ◽  
Cell Death ◽  
Photodynamic Therapy ◽  
Adaptive Immune Response ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Tumor Cell Death ◽  
Target Sites

Abstract Photodynamic therapy (PDT) is performed using a photosensitizer and light of specific wavelength in the presence of oxygen to generate singlet oxygen and reactive oxygen species(ROS) in the cancer cells. The accumulated photosensitizers in target sites induce ROS generation upon light activation, then the generated cytotoxic reactive oxygen species lead to tumor cell death via apoptosis or necrosis, and damages the target sites which results tumor destruction. As a consequence, the PDT-mediated cell death is associated with anti-tumor immune response. In this paper, the effects of PDT and immune response on tumors are reviewed. Activation of an immune response regarding the innate and adaptive immune response, interaction with immune cells and tumor cells that associated with antitumor efficacy of PDT are also discussed.

scholarly journals The Cisplatin-Derived Increase of Mitochondrial Reactive Oxygen Species Enhances the Effectiveness of Photodynamic Therapy via Transporter Regulation

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 918 ◽  
Author(s):  
Hiromi Kurokawa ◽  
Hiromu Ito ◽  
Hirofumi Matsui
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Cancer Cell ◽  
Aminolevulinic Acid ◽  
Reactive Oxygen ◽  
Peptide Transporter ◽  
Ros Generation ◽  
Oxygen Species ◽  
Mitochondrial Ros ◽  
Cancer Tissues

Photodynamic therapy (PDT) is a cancer treatment involving the generation of reactive oxygen species (ROS) by laser irradiation of porphyrins that accumulate in cancer tissues. 5-aminolevulinic acid (ALA), a porphyrin precursor, is often used as a photosensitizer. ALA is imported into cells via peptide transporter 1 (PEPT1), and porphyrin is exported via ATP-binding cassette member 2 of subfamily G (ABCG2). Thus, cancer cell-specific porphyrin accumulation involves regulation of both transporters to enhance the ALA-PDT effect. We reported previously that mitochondrial ROS (mitROS) upregulated PEPT1 expression and downregulated ABCG2 expression. Therefore, we propose that increasing mitROS production will enhance ALA-PDT cytotoxicity. Cisplatin is a chemotherapeutic drug that induces intracellular ROS generation. In this study, we investigated whether cisplatin-increased mitROS production in gastric cancer cell lines (RGK36 and RGK45) enhanced the cytotoxicity of ALA-PDT by regulation the expression of both PEPT1 and ABCG2. The results showed that cisplatin increased intracellular mitROS production in cancer but not normal cells (RGM1). PEPT1 was upregulated and ABCG2 downregulated in cancer cells treated with cisplatin. Moreover, intracellular porphyrin accumulation and ALA-PDT cytotoxicity increased. We conclude that cisplatin treatment increases the intracellular mitROS concentration and upregulates PEPT1 and downregulates ABCG2 expression.

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