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spelling paper:paper_14712407_v2_n1_p6_DeSiervi2023-06-08T16:17:20Z Delta-aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines. De Siervi, Adriana Vázquez, Elba Susana Rezával, Carolina Rossetti, María Victoria Batlle, Alcira María del Carmen aminolevulinic acid DNA DNA fragment glucose hemin protein p53 tetrazolium thiazole derivative thiazolyl blue article biosynthesis cell culture cell cycle dose response drug effect human liver cell carcinoma liver tumor metabolism Aminolevulinic Acid Carcinoma, Hepatocellular Cell Cycle DNA Fragmentation DNA, Neoplasm Dose-Response Relationship, Drug Glucose Hemin Humans Liver Neoplasms Tetrazolium Salts Thiazoles Tumor Cells, Cultured Tumor Suppressor Protein p53 BACKGROUND: Acute Intermittent Porphyria is a genetic disorder of heme metabolism, characterized by increased levels of porphyrin precursors, delta-aminolevulinic acid (ALA) and porphobilinogen (PBG). ALA has been reported to generate reactive oxygen species and to cause oxidative damage to proteins, subcellular structures and DNA. It is known that oxidative stress can induce apoptosis. The aim of this work was to study the cytotoxic effect of ALA on two hepatocarcinoma cell lines. RESULTS: We have determined the impact of ALA on HEP G2 and HEP 3B hepatocarcinoma cell lines survival as measured by the MTT assay. ALA proved to be cytotoxic in both cell lines however; HEP G2 was more sensitive to ALA than HEP 3B. Addition of hemin or glucose diminished ALA cytotoxicity in HEP G2 cells; instead it was enhanced in HEP 3B cells. Because apoptosis is usually associated with DNA fragmentation, the DNA of ALA treated and untreated cells were analyzed. The characteristic pattern of DNA fragmentation ladders was observed in ALA treated cells. To elucidate the mechanisms of ALA induced apoptosis, we examined its effect on p53 expression. No changes in p53 mRNA levels were observed after exposure of both cell lines to ALA for 24 h. CDK2 and CDK4 protein levels were reduced after ALA treatment at physiological concentrations. Fil:De Siervi, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Vazquez, E.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rezaval, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rossetti, M.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:del Batlle, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2002 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14712407_v2_n1_p6_DeSiervi http://hdl.handle.net/20.500.12110/paper_14712407_v2_n1_p6_DeSiervi
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic aminolevulinic acid
DNA
DNA fragment
glucose
hemin
protein p53
tetrazolium
thiazole derivative
thiazolyl blue
article
biosynthesis
cell culture
cell cycle
dose response
drug effect
human
liver cell carcinoma
liver tumor
metabolism
Aminolevulinic Acid
Carcinoma, Hepatocellular
Cell Cycle
DNA Fragmentation
DNA, Neoplasm
Dose-Response Relationship, Drug
Glucose
Hemin
Humans
Liver Neoplasms
Tetrazolium Salts
Thiazoles
Tumor Cells, Cultured
Tumor Suppressor Protein p53
spellingShingle aminolevulinic acid
DNA
DNA fragment
glucose
hemin
protein p53
tetrazolium
thiazole derivative
thiazolyl blue
article
biosynthesis
cell culture
cell cycle
dose response
drug effect
human
liver cell carcinoma
liver tumor
metabolism
Aminolevulinic Acid
Carcinoma, Hepatocellular
Cell Cycle
DNA Fragmentation
DNA, Neoplasm
Dose-Response Relationship, Drug
Glucose
Hemin
Humans
Liver Neoplasms
Tetrazolium Salts
Thiazoles
Tumor Cells, Cultured
Tumor Suppressor Protein p53
De Siervi, Adriana
Vázquez, Elba Susana
Rezával, Carolina
Rossetti, María Victoria
Batlle, Alcira María del Carmen
Delta-aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines.
topic_facet aminolevulinic acid
DNA
DNA fragment
glucose
hemin
protein p53
tetrazolium
thiazole derivative
thiazolyl blue
article
biosynthesis
cell culture
cell cycle
dose response
drug effect
human
liver cell carcinoma
liver tumor
metabolism
Aminolevulinic Acid
Carcinoma, Hepatocellular
Cell Cycle
DNA Fragmentation
DNA, Neoplasm
Dose-Response Relationship, Drug
Glucose
Hemin
Humans
Liver Neoplasms
Tetrazolium Salts
Thiazoles
Tumor Cells, Cultured
Tumor Suppressor Protein p53
description BACKGROUND: Acute Intermittent Porphyria is a genetic disorder of heme metabolism, characterized by increased levels of porphyrin precursors, delta-aminolevulinic acid (ALA) and porphobilinogen (PBG). ALA has been reported to generate reactive oxygen species and to cause oxidative damage to proteins, subcellular structures and DNA. It is known that oxidative stress can induce apoptosis. The aim of this work was to study the cytotoxic effect of ALA on two hepatocarcinoma cell lines. RESULTS: We have determined the impact of ALA on HEP G2 and HEP 3B hepatocarcinoma cell lines survival as measured by the MTT assay. ALA proved to be cytotoxic in both cell lines however; HEP G2 was more sensitive to ALA than HEP 3B. Addition of hemin or glucose diminished ALA cytotoxicity in HEP G2 cells; instead it was enhanced in HEP 3B cells. Because apoptosis is usually associated with DNA fragmentation, the DNA of ALA treated and untreated cells were analyzed. The characteristic pattern of DNA fragmentation ladders was observed in ALA treated cells. To elucidate the mechanisms of ALA induced apoptosis, we examined its effect on p53 expression. No changes in p53 mRNA levels were observed after exposure of both cell lines to ALA for 24 h. CDK2 and CDK4 protein levels were reduced after ALA treatment at physiological concentrations.
author De Siervi, Adriana
Vázquez, Elba Susana
Rezával, Carolina
Rossetti, María Victoria
Batlle, Alcira María del Carmen
author_facet De Siervi, Adriana
Vázquez, Elba Susana
Rezával, Carolina
Rossetti, María Victoria
Batlle, Alcira María del Carmen
author_sort De Siervi, Adriana
title Delta-aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines.
title_short Delta-aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines.
title_full Delta-aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines.
title_fullStr Delta-aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines.
title_full_unstemmed Delta-aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines.
title_sort delta-aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines.
publishDate 2002
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14712407_v2_n1_p6_DeSiervi
http://hdl.handle.net/20.500.12110/paper_14712407_v2_n1_p6_DeSiervi
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AT rezavalcarolina deltaaminolevulinicacidcytotoxiceffectsonhumanhepatocarcinomacelllines
AT rossettimariavictoria deltaaminolevulinicacidcytotoxiceffectsonhumanhepatocarcinomacelllines
AT batllealciramariadelcarmen deltaaminolevulinicacidcytotoxiceffectsonhumanhepatocarcinomacelllines
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