Ascorbic acid suppresses cell death in rat DS-sarcoma cancer cells induced by 5-aminolevulinic acid-based photodynamic therapy

2006 ◽  
Vol 40 (5) ◽  
pp. 827-836 ◽  
Author(s):  
Juergen Frank ◽  
Andrea Flaccus ◽  
Christine Schwarz ◽  
Christine Lambert ◽  
Hans K. Biesalski
Keyword(s):  
Cell Death ◽  
Ascorbic Acid ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Aminolevulinic Acid

scholarly journals Experimental investigation of a combinational iron chelating protoporphyrin IX prodrug for fluorescence detection and photodynamic therapy

2021 ◽  
Author(s):  
Anette Magnussen ◽  
Charlotte Reburn ◽  
Alexis Perry ◽  
Mark Wood ◽  
Alison Curnow
Keyword(s):  
Cell Death ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Iron Chelation ◽  
Squamous Carcinoma ◽  
Chelating Agent ◽  
Neutral Red ◽  
Squamous Carcinoma Cells

AbstractPhotodynamic therapy (PDT) is an oxygen-dependent, light-activated, and locally destructive drug treatment of cancer. Protoporphyrin IX (PpIX)-induced PDT exploits cancer cells’ own innate heme biosynthesis to hyper-accumulate the naturally fluorescent and photoactive precursor to heme, PpIX. This occurs as a result of administering heme precursors (e.g., aminolevulinic acid; ALA) because the final step of the pathway (the insertion of ferrous iron into PpIX by ferrochelatase to form heme) is relatively slow. Separate administration of an iron chelating agent has previously been demonstrated to significantly improve dermatological PpIX-PDT by further limiting heme production. A newly synthesized combinational iron chelating PpIX prodrug (AP2-18) has been assessed experimentally in cultured primary human cells of bladder and dermatological origin, as an alternative photosensitizing agent to ALA or its methyl or hexyl esters (MAL and HAL respectively) for photodetection/PDT. Findings indicated that the technique of iron chelation (either through the separate administration of the established hydroxypyridinone iron chelator CP94 or the just as effective combined AP2-18) did not enhance either PpIX fluorescence or PDT-induced (neutral red assessed) cell death in human primary normal and malignant bladder cells. However, 500 µM AP2-18 significantly increased PpIX accumulation and produced a trend of increased cell death within epithelial squamous carcinoma cells. PpIX accumulation destabilized the actin cytoskeleton in bladder cancer cells prior to PDT and resulted in caspase-3 cleavage/early apoptosis afterwards. AP2-18 iron chelation should continue to be investigated for the enhancement of dermatological PpIX-PDT applications but not bladder photodetection/PDT.

scholarly journals Systemic MEK inhibition enhances the efficacy of 5-aminolevulinic acid-photodynamic therapy

2019 ◽  
Vol 121 (9) ◽  
pp. 758-767 ◽  
Author(s):  
Vipin Shankar Chelakkot ◽  
Jayoti Som ◽  
Ema Yoshioka ◽  
Chantel P. Rice ◽  
Suzette G. Rutihinda ◽  
...  
Keyword(s):  
Cell Death ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Aminolevulinic Acid ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Mek Inhibitor ◽  
Ros Generation ◽  
Strong Basis ◽  
Mek Inhibition

Abstract Background Protoporphyrin IX (PpIX) gets accumulated preferentially in 5-aminolevulinic acid (5-ALA)-treated cancer cells. Photodynamic therapy (PDT) utilises the accumulated PpIX to trigger cell death by light-induced generation of reactive oxygen species (ROS). We previously demonstrated that oncogenic Ras/MEK decreases PpIX accumulation in cancer cells. Here, we investigated whether combined therapy with a MEK inhibitor would improve 5-ALA-PDT efficacy. Methods Cancer cells and mice models of cancer were treated with 5-ALA-PDT, MEK inhibitor or both MEK inhibitor and 5-ALA-PDT, and treatment efficacies were evaluated. Results Ras/MEK negatively regulates the cellular sensitivity to 5-ALA-PDT as cancer cells pre-treated with a MEK inhibitor were killed more efficiently by 5-ALA-PDT. MEK inhibition promoted 5-ALA-PDT-induced ROS generation and programmed cell death. Furthermore, the combination of 5-ALA-PDT and a systemic MEK inhibitor significantly suppressed tumour growth compared with either monotherapy in mouse models of cancer. Remarkably, 44% of mice bearing human colon tumours showed a complete response with the combined treatment. Conclusion We demonstrate a novel strategy to promote 5-ALA-PDT efficacy by targeting a cell signalling pathway regulating its sensitivity. This preclinical study provides a strong basis for utilising MEK inhibitors, which are approved for treating cancers, to enhance 5-ALA-PDT efficacy in the clinic.

scholarly journals ASCORBIC ACID SUPPRESSES CELL DEATH IN RAT DS‐SARCOMA CANCER CELLS AFTER ALA‐BASED PHOTODYNAMIC THERAPY

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Juergen Frank ◽  
Andrea Flaccus ◽  
Christine Schwarz ◽  
Christine Lambert ◽  
Hans Konrad Biesalski
Keyword(s):  
Cell Death ◽  
Ascorbic Acid ◽  
Photodynamic Therapy ◽  
Cancer Cells

scholarly journals eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhichao Fan ◽  
Xiaojun Cui ◽  
Dan Wei ◽  
Wei Liu ◽  
Buhong Li ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix

scholarly journals Molecular interaction and cellular studies on combination photodynamic therapy with rutoside for melanoma A375 cancer cells: an in vitro study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Khatereh Khorsandi ◽  
Reza Hosseinzadeh ◽  
Elham Chamani
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Cell Death ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Human Melanoma ◽  
Oxygen Species ◽  
Melanoma Cancer

Abstract Background Melanoma as a type of skin cancer, is associated with a high mortality rate. Therefore, early diagnosis and efficient surgical treatment of this disease is very important. Photodynamic therapy (PDT) involves the activation of a photosensitizer by light at specific wavelength that interacts with oxygen and creates singlet oxygen molecules or reactive oxygen species (ROS), which can lead to tumor cell death. Furthermore, one of the main approches in the prevention and treatment of various cancers is plant compounds application. Phenolic compounds are essential class of natural antioxidants, which play crucial biological roles such as anticancer effects. It was previously suggested that flavonoid such as rutoside could acts as pro-oxidant or antioxidant. Hence, in this study, we aimed to investigate the effect of rutoside on the combination therapy with methylene blue (MB) assisted by photodynamic treatment (PDT) using red light source (660 nm; power density: 30 mW/cm2) on A375 human melanoma cancer cells. Methods For this purpose, the A375 human melanoma cancer cell lines were treated by MB-PDT and rutoside. Clonogenic cell survival, MTT assay, and cell death mechanisms were also determined after performing the treatment. Subsequently, after the rutoside treatment and photodynamic therapy (PDT), cell cycle and intracellular reactive oxygen species (ROS) generation were measured. Results The obtained results showed that, MB-PDT and rutoside had better cytotoxic and antiprolifrative effects on A375 melanoma cancer cells compared to each free drug, whereas the cytotoxic effect on HDF human dermal fibroblast cell was not significant. MB-PDT and rutoside combination induced apoptosis and cell cycle arrest in the human melanoma cancer cell line. Intracellular ROS increased in A375 cancer cell line after the treatment with MB-PDT and rutoside. Conclusion The results suggest that, MB-PDT and rutoside could be considered as novel approaches as the combination treatment of melanoma cancer.

scholarly journals Effective Photodynamic Therapy for Colon Cancer Cells Using Chlorin e6 Coated Hyaluronic Acid-Based Carbon Nanotubes

2020 ◽  
Vol 21 (13) ◽  
pp. 4745 ◽  
Author(s):  
Prabhavathi Sundaram ◽  
Heidi Abrahamse
Keyword(s):  
Carbon Nanotubes ◽  
Colon Cancer ◽  
Cell Death ◽  
Photodynamic Therapy ◽  
Hyaluronic Acid ◽  
Cancer Cells ◽  
Chlorin E6 ◽  
Therapeutic Modality ◽  
Size Analysis ◽  
Colon Cancer Cells

Colon cancer is the third major cancer contributor to mortality worldwide. Nanosized particles have attracted attention due to their possible contribution towards cancer treatment and diagnosis. Photodynamic therapy (PDT) is a cancer therapeutic modality that involves a light source, a photosensitizer and reactive oxygen species. Carbon nanotubes are fascinating nanocarriers for drug delivery, cancer diagnosis and numerous potential applications due to their unique physicochemical properties. In this study, single walled carbon nanotubes (SWCNTs) were coupled with hyaluronic acid (HA) and chlorin e6 (Ce6) coated on the walls of SWCNTs. The newly synthesized nanobiocomposite was characterized using ultraviolet-visible spectroscopy, Fourier transform electron microscopy (FTIR), X-ray diffraction analysis (XRD), particle size analysis and zeta potential. The loading efficiency of the SWCNTs-HA for Ce6 was calculated. The toxicity of the nanobiocomposite was tested on colon cancer cells using PDT at a fluence of 5 J/cm2 and 10 J/cm2. After 24 h, cellular changes were observed via microscopy, LDH cytotoxicity assay and cell death induction using annexin propidium iodide. The results showed that the newly synthesized nanobiocomposite enhanced the ability of PDT to be a photosensitizer carrier and induced cell death in colon cancer cells.

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