scholarly journals Deferoxamine Iron Chelation Increases δ-Aminolevulinic Acid Induced Protoporphyrin IX in Xenograft Glioma Model

2010 ◽  
Vol 86 (2) ◽  
pp. 471-475 ◽  
Author(s):  
Pablo A. Valdés ◽  
Kimberley Samkoe ◽  
Julia A. O’Hara ◽  
David W. Roberts ◽  
Keith D. Paulsen ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Iron Chelation ◽  
Glioma Model

scholarly journals Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NFkB/MDR1 pathway

2020 ◽  
Author(s):  
Yoshifumi Mizobuchi ◽  
Kenji Shono ◽  
Izumi Yamaguchi ◽  
Kohei Nakajima ◽  
Yuri Fujiwara ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Surgical Intervention ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Multidrug Resistant ◽  
Down Regulation ◽  
Sonodynamic Therapy ◽  
Glioma Model ◽  
A Site ◽  
Mouse Glioma

Abstract Glioblastoma (GBM) has high mortality rates because of extremely therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) is an emerging and promising approach combined with low-intensity ultrasonication (US) and PpIX as a sonosensitizer for cancer, whereas its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, a MDR1 inhibitor and augmented anti-tumor effects of SDT. MDR1 down-regulation via Akt/NF-kB pathway by celecoxib was confirmed, using a NF-kB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via Akt/NF-kB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.

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 Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kenji Shono ◽  
Yoshifumi Mizobuchi ◽  
Izumi Yamaguchi ◽  
Kohei Nakajima ◽  
Yuri Fujiwara ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Surgical Intervention ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Multidrug Resistant ◽  
Down Regulation ◽  
Sonodynamic Therapy ◽  
Glioma Model ◽  
A Site ◽  
Mouse Glioma

AbstractGlioblastoma (GBM) has high mortality rates because of extreme therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) combined with low-intensity ultrasonication (US) and PpIX, as a sonosensitizer, is an emerging and promising approach, although its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented the anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, an MDR1 inhibitor, and augmented anti-tumor effects of SDT. MDR1 down-regulation via the Akt/NF-κB pathway by celecoxib was confirmed, using an NF-κB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via the Akt/NF-κB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.

Protoporphyrin IX Fluorescence Photobleaching and the Response of Rat Barrett's Esophagus Following 5-aminolevulinic Acid Photodynamic Therapy

2006 ◽  
Vol 82 (6) ◽  
pp. 1638 ◽  
Author(s):  
Ingrid A. Boere ◽  
Dominic J. Robinson ◽  
Henriette S. de Bruijn ◽  
Jolanda Kluin ◽  
Hugo W. Tilanus ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix

Kinetics of protoporphyrin IX formation in rat oral mucosa and skin after application of 5-aminolevulinic acid and its methylester

2004 ◽  
Author(s):  
Stefan Kristiansson ◽  
Asta Juzeniene ◽  
Petras Juzenas ◽  
Vladimir Iani ◽  
Lennart Löfgren ◽  
...  
Keyword(s):  
Oral Mucosa ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Kinetics Of

scholarly journals Two Subpopulations of Human Monocytes That Differ by Mitochondrial Membrane Potential

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 153
Author(s):  
Nikita G. Nikiforov ◽  
Anastasia Ryabova ◽  
Marina V. Kubekina ◽  
Igor D. Romanishkin ◽  
Kirill A. Trofimov ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Primary Culture ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Intima Media Thickness ◽  
Mtdna Mutations ◽  
Proinflammatory Activity

Atherosclerosis is associated with a chronic local inflammatory process in the arterial wall. Our previous studies have demonstrated the altered proinflammatory activity of circulating monocytes in patients with atherosclerosis. Moreover, atherosclerosis progression and monocyte proinflammatory activity were associated with mitochondrial DNA (mtDNA) mutations in circulating monocytes. The role of mitochondria in the immune system cells is currently well recognized. They can act as immunomodulators by releasing molecules associated with bacterial infection. We hypothesized that atherosclerosis can be associated with changes in the mitochondrial function of circulating monocytes. To test this hypothesis, we performed live staining of the mitochondria of CD14+ monocytes from healthy donors and atherosclerosis patients with MitoTracker Orange CMTMRos dye, which is sensitive to mitochondrial membrane potential. The intensity of such staining reflects mitochondrial functional activity. We found that parts of monocytes in the primary culture were characterized by low MitoTracker staining (MitoTracker-low monocytes). Such cells were morphologically similar to cells with normal staining and able to metabolize 5-aminolevulinic acid and accumulate the heme precursor protoporphyrin IX (PplX), indicative of partially preserved mitochondrial function. We assessed the proportion of MitoTracker-low monocytes in the primary culture for each study subject and compared the results with other parameters, such as monocyte ability to lipopolysaccharide (LPS)-induced proinflammatory activation and the intima-media thickness of carotid arteries. We found that the proportion of MitoTracker-low monocytes was associated with the presence of atherosclerotic plaques. An increased number of such monocytes in the primary culture was associated with a reduced proinflammatory activation ability of cells. The obtained results indicate the presence of circulating monocytes with mitochondrial dysfunction and the association of such cells with chronic inflammation and atherosclerosis development.

scholarly journals Chimeric Mouse With Humanized Liver Is an Appropriate Animal Model to Investigate Mode of Action for Porphyria-Mediated Hepatocytotoxicity

2021 ◽  
pp. 019262332110274
Author(s):  
Ayumi Eguchi ◽  
Satoki Fukunaga ◽  
Keiko Ogata ◽  
Masahiko Kushida ◽  
Hiroyuki Asano ◽  
...  
Keyword(s):  
Experimental Model ◽  
Mode Of Action ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Human Hepatocytes ◽  
Chimeric Mouse ◽  
Hepatocellular Injury ◽  
Hepatocyte Necrosis ◽  
Key Events

Porphyrinogenic compounds are known to induce porphyria-mediated hepatocellular injury and subsequent regenerative proliferation in rodents, ultimately leading to hepatocellular tumor induction. However, an appropriate in vivo experimental model to evaluate an effect of porphyrinogenic compounds on human liver has not been fully established. Recently, the chimeric mouse with humanized liver (PXB mice) became widely used as a humanized model in which human hepatocytes are transplanted. In the present study, we examined the utility of PXB mice as an in vivo experimental model to evaluate the key events of the porphyria-mediated cytotoxicity mode of action (MOA) in humans. The treatment of PXB mice with 5-aminolevulinic acid, a representative porphyrinogenic compound, for 28 days caused protoporphyrin IX accumulation, followed by hepatocyte necrosis, increased mitosis, and an increase in replicative DNA synthesis in human hepatocytes, indicative of cellular injury and regenerative proliferation, similar to findings in patients with porphyria or experimental porphyria models and corresponding to the key events of the MOA for porphyria-mediated hepatocellular carcinogenesis. We conclude that the PXB mouse is a useful model to evaluate the key events of the porphyria-mediated cytotoxicity MOA in humans and suggest the utility of PXB mice for clarifying the human relevancy of findings in mice.

scholarly journals Systematic Review and Meta-Analysis of In Vitro Anti-Human Cancer Experiments Investigating the Use of 5-Aminolevulinic Acid (5-ALA) for Photodynamic Therapy

2021 ◽  
Vol 14 (3) ◽  
pp. 229
Author(s):  
Yo Shinoda ◽  
Daitetsu Kato ◽  
Ryosuke Ando ◽  
Hikaru Endo ◽  
Tsutomu Takahashi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Photodynamic Therapy ◽  
Aminolevulinic Acid ◽  
Human Cancer ◽  
Meta Analysis ◽  
Protoporphyrin Ix ◽  
Cell Types ◽  
Amino Acid Derivative ◽  
Photodynamic Diagnosis

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT.

Sign in / Sign up

Export Citation Format

Share Document