scholarly journals Effect of 5-aminolevulinic acid-based photodynamic therapy via reactive oxygen species in human cholangiocarcinoma cells

2011 ◽  
pp. 1357 ◽  
Author(s):  
Chung-Wook Chung ◽  
Dae Hwan Kang
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Aminolevulinic Acid ◽  
Reactive Oxygen ◽  
Oxygen Species

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 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.

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.

scholarly journals Biotin-Containing Third Generation Glucoheptoamidated Polyamidoamine Dendrimer for 5-Aminolevulinic Acid Delivery System

2021 ◽  
Vol 22 (4) ◽  
pp. 1982 ◽  
Author(s):  
Aleksandra Kaczorowska ◽  
Małgorzata Malinga-Drozd ◽  
Wojciech Kałas ◽  
Marta Kopaczyńska ◽  
Stanisław Wołowiec ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Aminolevulinic Acid ◽  
Reactive Oxygen ◽  
Pamam Dendrimer ◽  
Variable Number ◽  
Amide Bond ◽  
Oxygen Species ◽  
Nmr Spectrum ◽  
Guest Molecules ◽  
Amine Groups

Polyamidoamine PAMAM dendrimer generation 3 (G3) was modified by attachment of biotin via amide bond and glucoheptoamidated by addition of α-D-glucoheptono-1,4-lacton to obtain a series of conjugates with a variable number of biotin residues. The composition of conjugates was determined by detailed 1-D and 2-D NMR spectroscopy to reveal the number of biotin residues, which were 1, 2, 4, 6, or 8, while the number of glucoheptoamide residues substituted most of the remaining primary amine groups of PAMAM G3. The conjugates were then used as host molecules to encapsulate the 5-aminolevulinic acid. The solubility of 5-aminolevulinic acid increased twice in the presence of the 5-mM guest in water. The interaction between host and guest was accompanied by deprotonation of the carboxylic group of 5-aminolevulinic acid and proton transfer into internal ternary nitrogen atoms of the guest as evidenced by a characteristic chemical shift of resonances in the 1H NMR spectrum of associates. The guest molecules were most likely encapsulated inside inner shell voids of the host. The number of guest molecules depended on the number of biotin residues of the host, which was 15 for non-biotin-containing glucoheptoamidated G3 down to 6 for glucoheptoamidated G3 with 8 biotin residues on the host surface. The encapsulates were not cytotoxic against Caco-2 cells up to 200-µM concentration in the dark. All encapsulates were able to deliver 5-aminolevulinic acid to cells but aqueous encapsulates were more active in this regard. Simultaneously, the reactive oxygen species were detected by staining with H2DCFDA in Caco-2 cells incubated with encapsulates. The amount of PpIX was sufficient for induction of reactive oxygen species upon 30-s illumination with a 655-nm laser beam.

CSIG-21. 5-ALA PDT AND TARGETING MEK/ERK SIGNALING ELICITS SYNERGISTIC ANTITUMOR EFFECTS IN DIFFUSE MIDLINE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi37-vi37
Author(s):  
Gabrielle Price ◽  
Daniel Rivera ◽  
Alexandros Bouras ◽  
Constantinos Hadjipanayis
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Proliferation ◽  
Aminolevulinic Acid ◽  
Tumor Therapy ◽  
Unmet Need ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Antitumor Effects ◽  
Genetically Engineered Mouse Model

Abstract Diffuse midline gliomas (DMGs) are highly invasive, unresectable tumors in children. To date, there is no effective treatment for DMGs. Fractionated radiotherapy (RT), currently the standard of care, has provided limited disease control. Current obstacles to treatment include the blood brain barrier (BBB) that limits systemic drug delivery, tumor therapy resistance, and brainstem infiltration. Given the unmet need for more effective DMG treatments, photodynamic therapy (PDT), with the precursor photosensitizing agent 5-aminolevulinic acid (5-ALA), is an oncologic treatment that holds promise. 5-ALA PDT of tumors occurs by targeting tumor cells that accumulate the 5-ALA metabolite, protoporphyrin IX (PPIX), with 635 nm light to create deadly reactive oxygen species (ROS). We explore the synergism of 5-ALA PDT with the MEK inhibitor, trametinib, since the RAS/MEK signaling pathway regulates tumor cell proliferation and survival and has been shown to therapeutically enhance PDT in select tumor models. We demonstrated that sub-micromolar levels of 5-ALA PDT and nanomolar levels of trametinib successfully decrease cell proliferation and induce apoptosis in multiple DMG cell lines. Cell viability assays revealed that drug response differs based on the histone mutation (H3.1 or H3.3) of the line. Mechanisms of decreased cell survival involves the generation of reactive oxygen species that induces programmed cell death. Through the use of a DMG genetically engineered mouse model, we also found 5-ALA PDT to induce apoptosis in vivo. The synergistic effects of MEK inhibition and 5-ALA PDT in vitro and apoptotic effects of 5-ALA PDT in vivo, highlights the potential therapeutic efficacy of this treatment modality.

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