Mechanisms involved in δ-aminolevulinic acid (ALA)-induced photosensitivity of tumor cells: Relation of ferrochelatase and uptake of ALA to the accumulation of protoporphyrin

Ohgari, Yoshiko; Nakayasu, Yuki; Kitajima, Sakihito; Sawamoto, Mari; Mori, Hajime; Shimokawa, Osamu; Matsui, Hirofumi; Taketani, Shigeru

doi:10.1016/j.bcp.2005.10.019

Cited by 140 publications

(133 citation statements)

References 30 publications

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“…On the other hand, it has been reported that ferrochelatase enzyme is decreased in its activity in cancer cells; therefore this contributes to the intracellular accumulation of PpIX (Li et al, 2001). Another factor that allows the biosynthesis of PpIX is the assimilation of ALA like as it was observed in murine fibrosarcoma cells MethA (Ohgari et al, 2005). Acording with the results obtainned in this work the chossen concentration of ALA was 125 µg/mL to B16F0 and 150 µg/mL to B16F10.…”

Section: Discussionsupporting

confidence: 80%

Isolation of Cellular Clones of Murine Melanoma Resistants to the Photodynamic Therapy and Characterization of Some Mechanisms Involved in the Radioresistance

Ramón-Gallegos¹,

Rosas-Flores²,

Barrera-Mendoza³

et al. 2011

Breakthroughs in Melanoma Research

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Section: Discussionsupporting

confidence: 80%

Isolation of Cellular Clones of Murine Melanoma Resistants to the Photodynamic Therapy and Characterization of Some Mechanisms Involved in the Radioresistance

Ramón-Gallegos¹,

Rosas-Flores²,

Barrera-Mendoza³

et al. 2011

Breakthroughs in Melanoma Research

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“…11,28 The detailed molecular mechanisms of selective accumulation in some tumor cells remain obscure. Several mechanisms have been hypothesized: altered activity of ferrochelatase, iron chelators, protoporphyrin IX synthesis, increased intracellular 5-ALA uptake, or disturbances in protoporphyrin IX outflow from malignant cells.…”

Section: Molecular Mechanisms Of 5-ala-induced Fluorescencementioning

confidence: 99%

Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

Marbacher

Klinger

Schwyzer

et al. 2014

FOC

136

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Object The accurate discrimination between tumor and normal tissue is crucial for determining how much to resect and therefore for the clinical outcome of patients with brain tumors. In recent years, guidance with 5-aminolevulinic acid (5-ALA)–induced intraoperative fluorescence has proven to be a useful surgical adjunct for gross-total resection of high-grade gliomas. The clinical utility of 5-ALA in resection of brain tumors other than glioblastomas has not yet been established. The authors assessed the frequency of positive 5-ALA fluorescence in a cohort of patients with primary brain tumors and metastases. Methods The authors conducted a single-center retrospective analysis of 531 patients with intracranial tumors treated by 5-ALA–guided resection or biopsy. They analyzed patient characteristics, preoperative and postoperative liver function test results, intraoperative tumor fluorescence, and histological data. They also screened discharge summaries for clinical adverse effects resulting from the administration of 5-ALA. Intraoperative qualitative 5-ALA fluorescence (none, mild, moderate, and strong) was documented by the surgeon and dichotomized into negative and positive fluorescence. Results A total of 458 cases qualified for final analysis. The highest percentage of 5-ALA–positive fluorescence in open resection was found in glioblastomas (96%, n = 99/103). Among other tumors, 5-ALA–positive fluorescence was detected in 88% (n = 21/32) of anaplastic gliomas (WHO Grade III), 40% (n = 8/19) of low-grade gliomas (WHO Grade II), no (n = 0/3) WHO Grade I gliomas, and 77% (n = 85/110) of meningiomas. Among metastases, the highest percentage of 5-ALA–positive fluorescence was detected in adenocarcinomas (48%, n = 13/27). Low rates or absence of positive fluorescence was found among pituitary adenomas (8%, n = 1/12) and schwannomas (0%, n = 0/7). Biopsies of high-grade primary brain tumors showed positive rates of fluorescence similar to those recorded for open resection. No clinical adverse effects associated with use of 5-ALA were observed. Only 1 patient had clinically silent transient elevation of liver enzymes. Conclusions Study findings suggest that the administration of 5-ALA as a surgical adjunct for resection and biopsy of primary brain tumors and brain metastases is safe. In light of the high rate of positive fluorescence in high-grade gliomas other than glioblastomas, meningiomas, and a variety of metastatic cancers, 5-ALA seems to be a promising tool for enhancing intraoperative identification of neoplastic tissue and optimizing the extent of resection.

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“…Non-photosensitive 5-ALA is metabolized into photosensitive protoporphyrin IX (PPIX) inside cells' mitochondria. PPIX preferentially accumulates into cancer cells due to their ferrochelatase deficiency [7]. In addition, 5-ALA is already efficiently used in tumor photodetection, notably in the case of glioblastoma surgical resection [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy

Coupienne

Bontems

Dewaele

et al. 2011

Biochemical Pharmacology

101

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To cite this version:Isabelle Coupienne Isabelle Coupienne, Sébastien Bontems, Michael Dewaele, Noemi Rubio, Yvette Habraken, et al.. NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy. Biochemical Pharmacology, Elsevier, 2011, 81 (5) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 AbstractGlioblastoma constitute the most frequent and deadliest brain tumors of astrocytic origin.They are very resistant to all current therapies and are associated with a huge rate of recurrence. In most cases, this type of tumor is characterized by a constitutive activation of the nuclear factor-kappaB (NF-B). This factor is known to be a key regulator of various physiological processes such as inflammation, immune response, cell growth or apoptosis. In the present study, we explored the role of NF-B activation in the sensitivity of human glioblastoma cells to a treatment by 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT). 5-ALA is a physiological compound widely used in PDT as well as in tumor photodetection (PDD). Our results show that inhibition of NF-κB improves glioblastoma cell death in response to 5-ALA-PDT. We then studied the molecular mechanisms underlying the cell death induced by PDT combined or not with NF-B inhibition. We found that apoptosis was induced by PDT but in an incomplete manner and that, unexpectedly, NF-B inhibition reduced its level. Oppositely PDT mainly induces necrosis in glioblastoma cells and NF-B is found to have anti-necrotic functions in this context. The autophagic flux was also enhanced as a result of 5-ALA-PDT and we demonstrate that stimulation of autophagy acts as a prosurvival mechanism confering protection against PDT-mediated necrosis. These data point out that 5-ALA-PDT has an interesting potential as a mean to treat glioblastoma and that inhibition of NF-B renders glioblastoma cells more sensitive to the treatment.

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Mechanisms involved in δ-aminolevulinic acid (ALA)-induced photosensitivity of tumor cells: Relation of ferrochelatase and uptake of ALA to the accumulation of protoporphyrin

Cited by 140 publications

References 30 publications

Isolation of Cellular Clones of Murine Melanoma Resistants to the Photodynamic Therapy and Characterization of Some Mechanisms Involved in the Radioresistance

Isolation of Cellular Clones of Murine Melanoma Resistants to the Photodynamic Therapy and Characterization of Some Mechanisms Involved in the Radioresistance

Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy

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