scholarly journals Reactivation of TAp73 tumor suppressor by protoporphyrin IX, a metabolite of aminolevulinic acid, induces apoptosis in TP53-deficient cancer cells

2018 ◽  
Author(s):  
Alicja Sznarkowska ◽  
Anna Kostecka ◽  
Anna Kawiak ◽  
Pilar Acedo ◽  
Mattia Lion ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Clinical Practice ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Ubiquitin Ligase ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Drug Repurposing ◽  
Functional Similarity ◽  
Photodynamic Therapy Of Cancer

AbstractBackgroundThe p73 protein is a tumor suppressor that shares structural and functional similarity with p53. p73 is expressed in two major isoforms; the TA isoform that interacts with p53 pathway, thus acting as tumor suppressor and the N-terminal truncated ΔN isoform that inhibits TAp73 and p53 and thus, acts as an oncogene.ResultsBy employing a drug repurposing approach, we found that protoporphyrin IX (PpIX), a metabolite of aminolevulinic acid (ALA) applied in photodynamic therapy of cancer, stabilizes TAp73 and activates TAp73-dependent apoptosis in cancer cells lacking p53. The mechanism of TAp73 activation is via disruption of TAp73/MDM2 and TAp73/MDMX interactions and inhibition of TAp73 degradation by ubiquitin ligase Itch.ConclusionOur findings may in future contribute to the successful repurposing of PpIX into clinical practice.

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 Correction to: Reactivation of TAp73 tumor suppressor by protoporphyrin IX, a metabolite of aminolevulinic acid, induces apoptosis in TP53-deficient cancer cells

Cell Division ◽  
2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Alicja Sznarkowska ◽  
Anna Kostecka ◽  
Anna Kawiak ◽  
Pilar Acedo ◽  
Mattia Lion ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Cells ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix

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 Reactivation of TAp73 tumor suppressor by protoporphyrin IX, a metabolite of aminolevulinic acid, induces apoptosis in TP53-deficient cancer cells

Cell Division ◽  
2018 ◽  
Vol 13 (1) ◽  
Author(s):  
Alicja Sznarkowska ◽  
Anna Kostecka ◽  
Anna Kawiak ◽  
Pilar Acedo ◽  
Mattia Lion ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Cells ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix

G-quadruplex/protoporphyrin IX-functionalized silver nanoconjugates for targeted cancer cell photodynamic therapy

RSC Advances ◽  
2016 ◽  
Vol 6 (99) ◽  
pp. 96942-96945 ◽  
Author(s):  
Jun Ai ◽  
Jing Li ◽  
Lu Ga ◽  
Guohong Yun ◽  
Li Xu ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cell Surface ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Specific Interaction ◽  
Protoporphyrin Ix ◽  
Photodynamic Therapy Of Cancer ◽  
G Quadruplex ◽  
New Type ◽  
Targeted Photodynamic Therapy

A new type of G-quadruplex/protoporphyrin IX-functionalized silver nanoconjugate was prepared and used for the targeted photodynamic therapy of cancer cells via the specific interaction between AS1411 and the nucleolin on the cell surface.

scholarly journals Enhanced lipid metabolism induces the sensitivity of dormant cancer cells to 5-aminolevulinic acid-based photodynamic therapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Taku Nakayama ◽  
Tomonori Sano ◽  
Yoshiki Oshimo ◽  
Chiaki Kawada ◽  
Moe Kasai ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Dependent Manner ◽  
Recurrent Cancer ◽  
Porphyrin Metabolism ◽  
Triacsin C ◽  
A Cell

AbstractCancer can develop into a recurrent metastatic disease with latency periods of years to decades. Dormant cancer cells, which represent a major cause of recurrent cancer, are relatively insensitive to most chemotherapeutic drugs and radiation. We previously demonstrated that cancer cells exhibited dormancy in a cell density-dependent manner. Dormant cancer cells exhibited increased porphyrin metabolism and sensitivity to 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). However, the metabolic changes in dormant cancer cells or the factors that enhance porphyrin metabolism have not been fully clarified. In this study, we revealed that lipid metabolism was increased in dormant cancer cells, leading to ALA-PDT sensitivity. We performed microarray analysis in non-dormant and dormant cancer cells and revealed that lipid metabolism was remarkably enhanced in dormant cancer cells. In addition, triacsin C, a potent inhibitor of acyl-CoA synthetases (ACSs), reduced protoporphyrin IX (PpIX) accumulation and decreased ALA-PDT sensitivity. We demonstrated that lipid metabolism including ACS expression was positively associated with PpIX accumulation. This research suggested that the enhancement of lipid metabolism in cancer cells induces PpIX accumulation and ALA-PDT sensitivity.

scholarly journals Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Taku Nakayama ◽  
Shimpei Otsuka ◽  
Tatsuya Kobayashi ◽  
Hodaka Okajima ◽  
Kentaro Matsumoto ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix

scholarly journals Enhanced Lipid Metabolism Induces the Sensitivity of Dormant Cancer Cells to 5-aminolevulinic acid-based Photodynamic Therapy

2021 ◽  
Author(s):  
Taku Nakayama ◽  
Tomonori Sano ◽  
Yoshiki Oshimo ◽  
Chiaki Kawada ◽  
Moe Kasai ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Dependent Manner ◽  
Recurrent Cancer ◽  
Porphyrin Metabolism ◽  
Triacsin C ◽  
A Cell

Abstract Cancer can develop into a recurrent metastatic disease with latency periods of years to decades. Dormant cancer cells, which represent a major cause of recurrent cancer, are relatively insensitive to most chemotherapeutic drugs and radiation. We previously demonstrated that cancer cells exhibited dormancy in a cell density-dependent manner. Dormant cancer cells exhibited increased porphyrin metabolism and sensitivity to 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). However, the metabolic changes in dormant cancer cells or the factors that enhance porphyrin metabolism have not been fully clarified. In this study, we revealed that lipid metabolism was increased in dormant cancer cells, leading to ALA-PDT sensitivity. We performed microarray analysis in non-dormant and dormant cancer cells and revealed that lipid metabolism was remarkably enhanced in dormant cancer cells. In addition, triacsin C, a potent inhibitor of acyl-CoA synthetases (ACSs), reduced protoporphyrin IX (PpIX) accumulation and decreased ALA-PDT sensitivity. We demonstrated that lipid metabolism including ACS expression was positively associated with PpIX accumulation. This research suggested that the enhancement of lipid metabolism in cancer cells induces PpIX accumulation and ALA-PDT sensitivity.

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