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.

scholarly journals The use of 5-aminolevulinic acid and its derivatives in photodynamic therapy and diagnosis

2018 ◽  
Vol 67 (4) ◽  
pp. 113-130
Author(s):  
Anna Romiszewska ◽  
Aneta Bombalska
Keyword(s):  
Photodynamic Therapy ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Photodynamic Diagnosis ◽  
Chemical Derivatives ◽  
Therapeutic Outcomes ◽  
Keywords Photodynamic Therapy ◽  
Therapy And Diagnosis ◽  
Derivatives Of ◽  
Ala Esters

5-aminolevulinic acid (5-ALA) is used as a drug in the photodynamic therapy (PDT) and photodynamic diagnosis (PDD) of cancer. Combined with irradiation at the appropriate wavelength, it is used as a photosensitizer precursor to identify/kill tumour cells. In cells, 5-aminolevulinic acid is converted to protoporphyrin IX (PpIX), which is the precursor of hemin. Internal application of 5-ALA induces the overproduction of the endogenous photosensitizer, PpIX, which can subsequently be activated by light at the appropriate wavelength. 5-ALA can be applied internally to trans-mutated areas or be injected directly into them. Chemical derivatives of 5ALA have the potential to improve bioavailability, enhance stability and lead to better therapeutic outcomes for treated patients. 5-ALA is currently the most commonly used drug in the photodynamic therapy and diagnosis (PDT/PDD) of cancers. Keywords: photodynamic therapy, photodynamic diagnosis, 5-aminolevulinic acid (5- ALA), esters of 5-aminolevulinic acid, cancer.

A vehicle for photodynamic therapy of skin cancer: influence of dimethylsulphoxide on 5-aminolevulinic acid in vitro cutaneous permeation and in vivo protoporphyrin IX accumulation determined by confocal microscopy

2000 ◽  
Vol 65 (3) ◽  
pp. 359-366 ◽  
Author(s):  
Fernanda Scarmato De Rosa ◽  
Juliana Maldonado Marchetti ◽  
José Antônio Thomazini ◽  
Antônio Cláudio Tedesco ◽  
Maria Vitória Lopes Badra Bentley
Keyword(s):  
Photodynamic Therapy ◽  
Skin Cancer ◽  
Confocal Microscopy ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix

scholarly journals MEK reduces cancer-specific PpIX accumulation through the RSK-ABCB1 and HIF-1α-FECH axes

2020 ◽  
Author(s):  
Vipin Shankar Chelakkot ◽  
Kaiwen Liu ◽  
Ema Yoshioka ◽  
Shaykat Saha ◽  
Danyang Xu ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Human Cancer ◽  
Protoporphyrin Ix ◽  
Mek Inhibitor ◽  
Photodynamic Diagnosis ◽  
Human Cancer Cell ◽  
Nih3t3 Cells ◽  
Human Cancer Cell Lines ◽  
Oncogenic Ras ◽  
Specific Accumulation

AbstractThe efficacy of aminolevulinic acid (5-ALA)-based photodynamic diagnosis (5-ALA-PDD) and photodynamic therapy (5-ALA-PDT) is dependent on the 5-ALA-induced cancer-specific accumulation of protoporphyrin IX (PpIX). We previously reported that inhibition of oncogenic Ras/MEK increases PpIX accumulation in cancer cells by reducing PpIX efflux through ATP-binding cassette sub-family B member 1 (ABCB1) as well as PpIX conversion to heme by ferrochelatase (FECH). Here, we sought to identify the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation via ABCB1 and FECH. First, we demonstrated that Ras/MEK activation reduced PpIX accumulation in RasV12-transformed NIH3T3 cells and HRAS transgenic mice. Knockdown of p90 ribosomal S6 kinases (RSK) 2, 3, or 4 increased PpIX accumulation in the RasV12-transformed NIH3T3 cells. Further, treatment with an RSK inhibitor reduced ABCB1 expression and increased PpIX accumulation. Moreover, HIF-1α expression was reduced when the RasV12-transformed NIH3T3 cells were treated with a MEK inhibitor, demonstrating that HIF-1α is a downstream element of MEK. HIF-1α inhibition decreased the activity of FECH and increased PpIX accumulation. Finally, we demonstrated the involvement of RSKs and HIF-1α in the regulation of PpIX accumulation in human cancer cell lines (DLD-1, SNB-75, Hs 578T, and MDA MB 231). These results demonstrate that the RSK-ABCB1 and HIF-1α-FECH axes are the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation.

scholarly journals Bystander Effects of Nitric Oxide in Cellular Models of Anti-Tumor Photodynamic Therapy

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1674 ◽  
Author(s):  
Jerzy Bazak ◽  
Witold Korytowski ◽  
Albert W. Girotti
Keyword(s):  
Nitric Oxide ◽  
Photodynamic Therapy ◽  
Aminolevulinic Acid ◽  
Human Cancer ◽  
Cell Types ◽  
Migration And Invasion ◽  
Bystander Effects ◽  
Human Cancer Cells ◽  
Cellular Models ◽  
Bystander Cells

Tumor cells exposed to stress-inducing radiotherapy or chemotherapy can send signals to non- or minimally exposed bystander cells. Bystander effects of ionizing radiation are well established, but little is known about such effects in non-ionizing photodynamic therapy (PDT). Our previous studies revealed that several cancer cell types upregulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) after a moderate 5-aminolevulinic acid (ALA)-based PDT challenge. The NO signaled for cell resistance to photokilling as well as greater growth, migration and invasion of surviving cells. Based on this work, we hypothesized that diffusible NO produced by PDT-targeted cells in a tumor might elicit pro-growth/migration responses in non-targeted bystander cells. In the present study, we tested this using a novel approach, in which ALA-PDT-targeted human cancer cells on culture dishes (prostate PC3, breast MDA-MB-231, glioma U87, or melanoma BLM) were initially segregated from non-targeted bystanders via impermeable silicone-rimmed rings. Several hours after LED irradiation, rings were removed, and both cell populations analyzed for various post-hν responses. For a moderate and uniform level of targeted cell killing by PDT (~25%), bystander proliferation and migration were both enhanced. Enhancement correlated with iNOS/NO upregulation in surviving targeted cells in the following order: PC3 > MDA-MB-231 > U87 > BLM. If occurring in an actual tumor PDT setting and not suppressed (e.g., by iNOS activity or transcription inhibitors), then such effects could compromise treatment efficacy or even stimulate disease progression if PDT’s anti-tumor potency is not great enough.

scholarly journals MEK reduces cancer-specific PpIX accumulation through the RSK-ABCB1 and HIF-1α-FECH axes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vipin Shankar Chelakkot ◽  
Kaiwen Liu ◽  
Ema Yoshioka ◽  
Shaykat Saha ◽  
Danyang Xu ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Human Cancer ◽  
Protoporphyrin Ix ◽  
Mek Inhibitor ◽  
Photodynamic Diagnosis ◽  
Human Cancer Cell ◽  
Nih3t3 Cells ◽  
Human Cancer Cell Lines ◽  
Oncogenic Ras ◽  
Specific Accumulation

AbstractThe efficacy of aminolevulinic acid (5-ALA)-based photodynamic diagnosis (5-ALA-PDD) and photodynamic therapy (5-ALA-PDT) is dependent on 5-ALA-induced cancer-specific accumulation of protoporphyrin IX (PpIX). We previously reported that inhibition of oncogenic Ras/MEK increases PpIX accumulation in cancer cells by reducing PpIX efflux through ATP-binding cassette sub-family B member 1 (ABCB1) and ferrochelatase (FECH)-catalysed PpIX conversion to haem. Here, we sought to identify the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation via ABCB1 and FECH. First, we demonstrated that Ras/MEK activation reduced PpIX accumulation in RasV12-transformed NIH3T3 cells and HRAS transgenic mice. Knockdown of p90 ribosomal S6 kinases (RSK) 2, 3, or 4 increased PpIX accumulation in RasV12-transformed NIH3T3 cells. Further, treatment with an RSK inhibitor reduced ABCB1 expression and increased PpIX accumulation. Moreover, HIF-1α expression was reduced when RasV12-transformed NIH3T3 cells were treated with a MEK inhibitor, demonstrating that HIF-1α is a downstream element of MEK. HIF-1α inhibition decreased FECH activity and increased PpIX accumulation. Finally, we demonstrated the involvement of RSKs and HIF-1α in the regulation of PpIX accumulation in human cancer cell lines. These results demonstrate that the RSK-ABCB1 and HIF-1α-FECH axes are the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation.

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