Delta-aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines.
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...
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todo:paper_14712407_v2_n1_p6_DeSiervi2023-10-03T16:17:53Z Delta-aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines. De Siervi, A. Vazquez, E.S. Rezaval, C. Rossetti, M.V. del Batlle, A.M. 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. JOUR English info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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) |
| language |
English |
| orig_language_str_mv |
English |
| 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, A. Vazquez, E.S. Rezaval, C. Rossetti, M.V. del Batlle, A.M. 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. |
| format |
JOUR |
| author |
De Siervi, A. Vazquez, E.S. Rezaval, C. Rossetti, M.V. del Batlle, A.M. |
| author_facet |
De Siervi, A. Vazquez, E.S. Rezaval, C. Rossetti, M.V. del Batlle, A.M. |
| author_sort |
De Siervi, A. |
| 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. |
| url |
http://hdl.handle.net/20.500.12110/paper_14712407_v2_n1_p6_DeSiervi |
| work_keys_str_mv |
AT desiervia deltaaminolevulinicacidcytotoxiceffectsonhumanhepatocarcinomacelllines AT vazquezes deltaaminolevulinicacidcytotoxiceffectsonhumanhepatocarcinomacelllines AT rezavalc deltaaminolevulinicacidcytotoxiceffectsonhumanhepatocarcinomacelllines AT rossettimv deltaaminolevulinicacidcytotoxiceffectsonhumanhepatocarcinomacelllines AT delbatlleam deltaaminolevulinicacidcytotoxiceffectsonhumanhepatocarcinomacelllines |
| _version_ |
1807318695010107392 |