Evaluation of Aflatoxin M1 Effects on the Metabolomic and Cytokinomic Profiling of a Hepatoblastoma Cell Line

Hepatoblastoma incidence has been associated with different environmental factors even if no data are reported about a correlation between aflatoxin exposure and hepatoblastoma initiation. Considering that hepatoblastoma develops in infants and children and aflatoxin M1 (AFM1), the aflatoxin B1 (AFB...

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Main Authors: Silvia Marchese, Angela Sorice, Andrea Ariano, Salvatore Florio, Alfredo Budillon, Susan Costantini, Lorella Severino
Format: Article
Language:English
Published: MDPI AG 2018-10-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/10/11/436
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author Silvia Marchese
Angela Sorice
Andrea Ariano
Salvatore Florio
Alfredo Budillon
Susan Costantini
Lorella Severino
author_facet Silvia Marchese
Angela Sorice
Andrea Ariano
Salvatore Florio
Alfredo Budillon
Susan Costantini
Lorella Severino
author_sort Silvia Marchese
collection DOAJ
description Hepatoblastoma incidence has been associated with different environmental factors even if no data are reported about a correlation between aflatoxin exposure and hepatoblastoma initiation. Considering that hepatoblastoma develops in infants and children and aflatoxin M1 (AFM1), the aflatoxin B1 (AFB1) hydroxylated metabolite, can be present in mothers&#8217; milk and in marketed milk products, in this study we decided to test the effects of AFM1 on a hepatoblastoma cell line (HepG2). Firstly, we evaluated the effects of AFM1 on the cell viability, apoptosis, cell cycle, and metabolomic and cytokinomic profile of HepG2 cells after treatment. AFM1 induced: (1) a decrease of HepG2 cell viability, reaching IC<sub>50</sub> at 9 &#181;M; (2) the blocking of the cell cycle in the G0/G1 phase; (3) the decrease of formiate levels and incremented level of some amino acids and metabolites in HepG2 cells after treatment; and (4) the increase of the concentration of three pro-inflammatory cytokines, IL-6, IL-8, and TNF-&#945;, and the decrease of the anti-inflammatory interleukin, IL-4. Our results show that AFM1 inhibited the growth of HepG2 cells, inducing both a modulation of the lipidic, glycolytic, and amino acid metabolism and an increase of the inflammatory status of these cells.
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spelling doaj.art-68dc84c7bdb64e4689288dc49d0df63e2022-12-22T02:54:46ZengMDPI AGToxins2072-66512018-10-01101143610.3390/toxins10110436toxins10110436Evaluation of Aflatoxin M1 Effects on the Metabolomic and Cytokinomic Profiling of a Hepatoblastoma Cell LineSilvia Marchese0Angela Sorice1Andrea Ariano2Salvatore Florio3Alfredo Budillon4Susan Costantini5Lorella Severino6Unità di Farmacologia e Tossicologia—Dipartimento di Medicina Veterinaria e Produzioni Animali, Università degli Studi di Napoli “Federico II”, 80138 Napoli, ItalyUnità di Farmacologia Sperimentale, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, ItalyUnità di Farmacologia e Tossicologia—Dipartimento di Medicina Veterinaria e Produzioni Animali, Università degli Studi di Napoli “Federico II”, 80138 Napoli, ItalyUnità di Farmacologia e Tossicologia—Dipartimento di Medicina Veterinaria e Produzioni Animali, Università degli Studi di Napoli “Federico II”, 80138 Napoli, ItalyUnità di Farmacologia Sperimentale, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, ItalyUnità di Farmacologia Sperimentale, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, ItalyUnità di Farmacologia e Tossicologia—Dipartimento di Medicina Veterinaria e Produzioni Animali, Università degli Studi di Napoli “Federico II”, 80138 Napoli, ItalyHepatoblastoma incidence has been associated with different environmental factors even if no data are reported about a correlation between aflatoxin exposure and hepatoblastoma initiation. Considering that hepatoblastoma develops in infants and children and aflatoxin M1 (AFM1), the aflatoxin B1 (AFB1) hydroxylated metabolite, can be present in mothers&#8217; milk and in marketed milk products, in this study we decided to test the effects of AFM1 on a hepatoblastoma cell line (HepG2). Firstly, we evaluated the effects of AFM1 on the cell viability, apoptosis, cell cycle, and metabolomic and cytokinomic profile of HepG2 cells after treatment. AFM1 induced: (1) a decrease of HepG2 cell viability, reaching IC<sub>50</sub> at 9 &#181;M; (2) the blocking of the cell cycle in the G0/G1 phase; (3) the decrease of formiate levels and incremented level of some amino acids and metabolites in HepG2 cells after treatment; and (4) the increase of the concentration of three pro-inflammatory cytokines, IL-6, IL-8, and TNF-&#945;, and the decrease of the anti-inflammatory interleukin, IL-4. Our results show that AFM1 inhibited the growth of HepG2 cells, inducing both a modulation of the lipidic, glycolytic, and amino acid metabolism and an increase of the inflammatory status of these cells.https://www.mdpi.com/2072-6651/10/11/436aflatoxin M1metabolomecytokinomehepatoblastoma
spellingShingle Silvia Marchese
Angela Sorice
Andrea Ariano
Salvatore Florio
Alfredo Budillon
Susan Costantini
Lorella Severino
Evaluation of Aflatoxin M1 Effects on the Metabolomic and Cytokinomic Profiling of a Hepatoblastoma Cell Line
Toxins
aflatoxin M1
metabolome
cytokinome
hepatoblastoma
title Evaluation of Aflatoxin M1 Effects on the Metabolomic and Cytokinomic Profiling of a Hepatoblastoma Cell Line
title_full Evaluation of Aflatoxin M1 Effects on the Metabolomic and Cytokinomic Profiling of a Hepatoblastoma Cell Line
title_fullStr Evaluation of Aflatoxin M1 Effects on the Metabolomic and Cytokinomic Profiling of a Hepatoblastoma Cell Line
title_full_unstemmed Evaluation of Aflatoxin M1 Effects on the Metabolomic and Cytokinomic Profiling of a Hepatoblastoma Cell Line
title_short Evaluation of Aflatoxin M1 Effects on the Metabolomic and Cytokinomic Profiling of a Hepatoblastoma Cell Line
title_sort evaluation of aflatoxin m1 effects on the metabolomic and cytokinomic profiling of a hepatoblastoma cell line
topic aflatoxin M1
metabolome
cytokinome
hepatoblastoma
url https://www.mdpi.com/2072-6651/10/11/436
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