Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest

Cervical cancer (CC) is one of the most common cancers in women, and is linked to human papillomavirus (HPV) infection. The virus oncoprotein E6 binds to p53, resulting in its degradation and allowing uncontrolled cell proliferation. Meanwhile, the HPV E7 protein maintains host cell differentiation...

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Main Authors: Claudia Vanessa Arellano-Gutiérrez, Laura Itzel Quintas-Granados, Hernán Cortés, Manuel González del Carmen, Gerardo Leyva-Gómez, Lilia Patricia Bustamante-Montes, Miguel Rodríguez-Morales, Israel López-Reyes, Juan Ramón Padilla-Mendoza, Lorena Rodríguez-Páez, Gabriela Figueroa-González, Octavio Daniel Reyes-Hernández
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Current Issues in Molecular Biology
Subjects:
Online Access:https://www.mdpi.com/1467-3045/44/5/139
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author Claudia Vanessa Arellano-Gutiérrez
Laura Itzel Quintas-Granados
Hernán Cortés
Manuel González del Carmen
Gerardo Leyva-Gómez
Lilia Patricia Bustamante-Montes
Miguel Rodríguez-Morales
Israel López-Reyes
Juan Ramón Padilla-Mendoza
Lorena Rodríguez-Páez
Gabriela Figueroa-González
Octavio Daniel Reyes-Hernández
author_facet Claudia Vanessa Arellano-Gutiérrez
Laura Itzel Quintas-Granados
Hernán Cortés
Manuel González del Carmen
Gerardo Leyva-Gómez
Lilia Patricia Bustamante-Montes
Miguel Rodríguez-Morales
Israel López-Reyes
Juan Ramón Padilla-Mendoza
Lorena Rodríguez-Páez
Gabriela Figueroa-González
Octavio Daniel Reyes-Hernández
author_sort Claudia Vanessa Arellano-Gutiérrez
collection DOAJ
description Cervical cancer (CC) is one of the most common cancers in women, and is linked to human papillomavirus (HPV) infection. The virus oncoprotein E6 binds to p53, resulting in its degradation and allowing uncontrolled cell proliferation. Meanwhile, the HPV E7 protein maintains host cell differentiation by targeting retinoblastoma tumor suppressor. The host cell can ubiquitinate E6 and E7 through UBE2L3, whose expression depends on the interaction between the aryl hydrocarbon receptor (AhR) with Xenobiotic Responsive Elements (XREs) located in the <i>UBE2L3</i> gene promoter. In this study, we used cell culture to determine the effect of indole-3-carbinol (I3C) over cellular viability, apoptosis, cell proliferation, and mRNA levels of <i>UBE2L3</i> and <i>CYP1A1.</i> In addition, patients’ samples were used to determine the mRNA levels of <i>UBE2L3</i> and <i>CYP1A1</i> genes. We found that I3C promotes the activation of AhR and decreases cell proliferation, possibly through <i>UBE2L3</i> mRNA induction, which would result in the ubiquitination of HPV E7. Since there is a strong requirement for selective and cost-effective cancer treatments, natural AhR ligands such as I3C could represent a novel strategy for cancer treatment.
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spelling doaj.art-b64f6340fc884c13ad12e6f46b25594c2023-11-23T10:32:17ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-05-014452054206810.3390/cimb44050139Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation ArrestClaudia Vanessa Arellano-Gutiérrez0Laura Itzel Quintas-Granados1Hernán Cortés2Manuel González del Carmen3Gerardo Leyva-Gómez4Lilia Patricia Bustamante-Montes5Miguel Rodríguez-Morales6Israel López-Reyes7Juan Ramón Padilla-Mendoza8Lorena Rodríguez-Páez9Gabriela Figueroa-González10Octavio Daniel Reyes-Hernández11Laboratorio de Bioquímica Farmacológica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoUnidad de Estudios Superiores Tultitlán, Universidad Mexiquense del Bicentenario, Estado de Mexico 54910, MexicoLaboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México 14389, MexicoFacultad de Medicina, Universidad Veracruzana, Ciudad Mendoza 94740, MexicoDepartamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, MexicoDecanatura Ciencias de la Salud, Universidad Autónoma de Guadalajara, Guadalajara 44670, MexicoLicenciatura en Médico Cirujano-INIES CUI, Ixtlahuaca Jiquipilco, San Pedro, Ixtlahuaca de Rayón 50740, MexicoColegio de Ciencias y Humanidades, Plantel Cuautepec, Universidad Autónoma de la Ciudad de México, Ciudad de México 6720, MexicoDepartamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados (CINVESTAV-IPN), Ciudad de México 07360, MexicoLaboratorio de Bioquímica Farmacológica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoLaboratorio de Farmacogenética, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, MexicoLaboratorio de Biología Molecular del Cáncer, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, MexicoCervical cancer (CC) is one of the most common cancers in women, and is linked to human papillomavirus (HPV) infection. The virus oncoprotein E6 binds to p53, resulting in its degradation and allowing uncontrolled cell proliferation. Meanwhile, the HPV E7 protein maintains host cell differentiation by targeting retinoblastoma tumor suppressor. The host cell can ubiquitinate E6 and E7 through UBE2L3, whose expression depends on the interaction between the aryl hydrocarbon receptor (AhR) with Xenobiotic Responsive Elements (XREs) located in the <i>UBE2L3</i> gene promoter. In this study, we used cell culture to determine the effect of indole-3-carbinol (I3C) over cellular viability, apoptosis, cell proliferation, and mRNA levels of <i>UBE2L3</i> and <i>CYP1A1.</i> In addition, patients’ samples were used to determine the mRNA levels of <i>UBE2L3</i> and <i>CYP1A1</i> genes. We found that I3C promotes the activation of AhR and decreases cell proliferation, possibly through <i>UBE2L3</i> mRNA induction, which would result in the ubiquitination of HPV E7. Since there is a strong requirement for selective and cost-effective cancer treatments, natural AhR ligands such as I3C could represent a novel strategy for cancer treatment.https://www.mdpi.com/1467-3045/44/5/139cervical cancerindole-3-carbinol<i>UBE2L3</i>cellular proliferation
spellingShingle Claudia Vanessa Arellano-Gutiérrez
Laura Itzel Quintas-Granados
Hernán Cortés
Manuel González del Carmen
Gerardo Leyva-Gómez
Lilia Patricia Bustamante-Montes
Miguel Rodríguez-Morales
Israel López-Reyes
Juan Ramón Padilla-Mendoza
Lorena Rodríguez-Páez
Gabriela Figueroa-González
Octavio Daniel Reyes-Hernández
Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest
Current Issues in Molecular Biology
cervical cancer
indole-3-carbinol
<i>UBE2L3</i>
cellular proliferation
title Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest
title_full Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest
title_fullStr Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest
title_full_unstemmed Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest
title_short Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest
title_sort indole 3 carbinol a phytochemical aryl hydrocarbon receptor ligand induces the mrna overexpression of ube2l3 and cell proliferation arrest
topic cervical cancer
indole-3-carbinol
<i>UBE2L3</i>
cellular proliferation
url https://www.mdpi.com/1467-3045/44/5/139
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