Sensitivity to ALA-PDT of cell lines with different nitric oxide production and resistance to NO cytotoxicity

In this work, we studied the in vitro interactions between aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) and nitric oxide (NO), as well as the interactions between ALA, porphyrins and some NO donors and precursors. We employed three murine adenocarcinoma cell lines: LM2, which does n...

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Autores principales: Di Venosa, G., Perotti, C., Fukuda, H., Batlle, A., Casas, A.
Formato: JOUR
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_10111344_v80_n3_p195_DiVenosa
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spelling todo:paper_10111344_v80_n3_p195_DiVenosa2023-10-03T15:56:15Z Sensitivity to ALA-PDT of cell lines with different nitric oxide production and resistance to NO cytotoxicity Di Venosa, G. Perotti, C. Fukuda, H. Batlle, A. Casas, A. 5-Aminolevulinic acid ALA-PDT Nitric oxide Photodynamic therapy aminolevulinic acid arginine hydrolyase nitric oxide nitric oxide donor nitroprusside sodium adenocarcinoma animal cell animal experiment animal model article biosynthesis blood flow cancer therapy carcinoma cell cell protection controlled study cross resistance cytotoxicity drug mechanism drug response enzyme inhibition hypothesis in vitro study in vivo study molecular interaction mouse nonhuman photodynamic therapy priority journal sensitivity analysis Adenocarcinoma Aminolevulinic Acid Animals Cell Line Cell Line, Tumor Cell Survival Female L Cells (Cell Line) Mammary Neoplasms, Animal Mice Mice, Inbred BALB C Nitric Oxide Nitric Oxide Donors Photochemotherapy Porphyrins Murinae In this work, we studied the in vitro interactions between aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) and nitric oxide (NO), as well as the interactions between ALA, porphyrins and some NO donors and precursors. We employed three murine adenocarcinoma cell lines: LM2, which does not produce NO; LM3, which produces NO, and LM3-SNP, a variant of LM3 resistant to NO producing the same amount of NO as the parental. We did not find cross-resistance between NO-induced cytotoxicity and ALA-PDT. In spite of the lower porphyrin synthesis, LM2 cells show the highest sensitivity to ALA-PDT. However, we hypothesised that this is not related to the lack of endogenous NO production, because modulation of NO levels did not modify the response to PDT in any of the cell lines. Two unexpected results were found: the enhancement of NO production from the donor sodium nitroprusside (SNP) induced by ALA in both cells and medium, and the inhibition by ALA of NO production from arginine. We also found that SNP strongly protected the cells from ALA-PDT by impairing porphyrin biosynthesis as a consequence of an inhibition of the enzyme ALA dehydratase. We were not able to evaluate the action of NO derived from SNP because of the unexpected porphyrin impairment. On the other hand, impairment of NO from Arginine driven by ALA, although not modulating in vitro the ALA-PDT response, by increasing in vivo blood flow, may be contributing to the mechanism of tumour cures. © 2005 Elsevier B.V. All rights reserved. Fil:Di Venosa, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Perotti, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fukuda, H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Batlle, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Casas, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_10111344_v80_n3_p195_DiVenosa
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic 5-Aminolevulinic acid
ALA-PDT
Nitric oxide
Photodynamic therapy
aminolevulinic acid
arginine
hydrolyase
nitric oxide
nitric oxide donor
nitroprusside sodium
adenocarcinoma
animal cell
animal experiment
animal model
article
biosynthesis
blood flow
cancer therapy
carcinoma cell
cell protection
controlled study
cross resistance
cytotoxicity
drug mechanism
drug response
enzyme inhibition
hypothesis
in vitro study
in vivo study
molecular interaction
mouse
nonhuman
photodynamic therapy
priority journal
sensitivity analysis
Adenocarcinoma
Aminolevulinic Acid
Animals
Cell Line
Cell Line, Tumor
Cell Survival
Female
L Cells (Cell Line)
Mammary Neoplasms, Animal
Mice
Mice, Inbred BALB C
Nitric Oxide
Nitric Oxide Donors
Photochemotherapy
Porphyrins
Murinae
spellingShingle 5-Aminolevulinic acid
ALA-PDT
Nitric oxide
Photodynamic therapy
aminolevulinic acid
arginine
hydrolyase
nitric oxide
nitric oxide donor
nitroprusside sodium
adenocarcinoma
animal cell
animal experiment
animal model
article
biosynthesis
blood flow
cancer therapy
carcinoma cell
cell protection
controlled study
cross resistance
cytotoxicity
drug mechanism
drug response
enzyme inhibition
hypothesis
in vitro study
in vivo study
molecular interaction
mouse
nonhuman
photodynamic therapy
priority journal
sensitivity analysis
Adenocarcinoma
Aminolevulinic Acid
Animals
Cell Line
Cell Line, Tumor
Cell Survival
Female
L Cells (Cell Line)
Mammary Neoplasms, Animal
Mice
Mice, Inbred BALB C
Nitric Oxide
Nitric Oxide Donors
Photochemotherapy
Porphyrins
Murinae
Di Venosa, G.
Perotti, C.
Fukuda, H.
Batlle, A.
Casas, A.
Sensitivity to ALA-PDT of cell lines with different nitric oxide production and resistance to NO cytotoxicity
topic_facet 5-Aminolevulinic acid
ALA-PDT
Nitric oxide
Photodynamic therapy
aminolevulinic acid
arginine
hydrolyase
nitric oxide
nitric oxide donor
nitroprusside sodium
adenocarcinoma
animal cell
animal experiment
animal model
article
biosynthesis
blood flow
cancer therapy
carcinoma cell
cell protection
controlled study
cross resistance
cytotoxicity
drug mechanism
drug response
enzyme inhibition
hypothesis
in vitro study
in vivo study
molecular interaction
mouse
nonhuman
photodynamic therapy
priority journal
sensitivity analysis
Adenocarcinoma
Aminolevulinic Acid
Animals
Cell Line
Cell Line, Tumor
Cell Survival
Female
L Cells (Cell Line)
Mammary Neoplasms, Animal
Mice
Mice, Inbred BALB C
Nitric Oxide
Nitric Oxide Donors
Photochemotherapy
Porphyrins
Murinae
description In this work, we studied the in vitro interactions between aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) and nitric oxide (NO), as well as the interactions between ALA, porphyrins and some NO donors and precursors. We employed three murine adenocarcinoma cell lines: LM2, which does not produce NO; LM3, which produces NO, and LM3-SNP, a variant of LM3 resistant to NO producing the same amount of NO as the parental. We did not find cross-resistance between NO-induced cytotoxicity and ALA-PDT. In spite of the lower porphyrin synthesis, LM2 cells show the highest sensitivity to ALA-PDT. However, we hypothesised that this is not related to the lack of endogenous NO production, because modulation of NO levels did not modify the response to PDT in any of the cell lines. Two unexpected results were found: the enhancement of NO production from the donor sodium nitroprusside (SNP) induced by ALA in both cells and medium, and the inhibition by ALA of NO production from arginine. We also found that SNP strongly protected the cells from ALA-PDT by impairing porphyrin biosynthesis as a consequence of an inhibition of the enzyme ALA dehydratase. We were not able to evaluate the action of NO derived from SNP because of the unexpected porphyrin impairment. On the other hand, impairment of NO from Arginine driven by ALA, although not modulating in vitro the ALA-PDT response, by increasing in vivo blood flow, may be contributing to the mechanism of tumour cures. © 2005 Elsevier B.V. All rights reserved.
format JOUR
author Di Venosa, G.
Perotti, C.
Fukuda, H.
Batlle, A.
Casas, A.
author_facet Di Venosa, G.
Perotti, C.
Fukuda, H.
Batlle, A.
Casas, A.
author_sort Di Venosa, G.
title Sensitivity to ALA-PDT of cell lines with different nitric oxide production and resistance to NO cytotoxicity
title_short Sensitivity to ALA-PDT of cell lines with different nitric oxide production and resistance to NO cytotoxicity
title_full Sensitivity to ALA-PDT of cell lines with different nitric oxide production and resistance to NO cytotoxicity
title_fullStr Sensitivity to ALA-PDT of cell lines with different nitric oxide production and resistance to NO cytotoxicity
title_full_unstemmed Sensitivity to ALA-PDT of cell lines with different nitric oxide production and resistance to NO cytotoxicity
title_sort sensitivity to ala-pdt of cell lines with different nitric oxide production and resistance to no cytotoxicity
url http://hdl.handle.net/20.500.12110/paper_10111344_v80_n3_p195_DiVenosa
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AT perottic sensitivitytoalapdtofcelllineswithdifferentnitricoxideproductionandresistancetonocytotoxicity
AT fukudah sensitivitytoalapdtofcelllineswithdifferentnitricoxideproductionandresistancetonocytotoxicity
AT batllea sensitivitytoalapdtofcelllineswithdifferentnitricoxideproductionandresistancetonocytotoxicity
AT casasa sensitivitytoalapdtofcelllineswithdifferentnitricoxideproductionandresistancetonocytotoxicity
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