Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest
Por:
Arellano-Gutiérrez C.V., Quintas-Granados L.I., Cortes, Hernan, Del Carmen M.G., Leyva-Gomez, Gerardo, Bustamante-Montes L.P., Rodriguez-Morales, Miguel, Lopez-Reyes, Israel, Padilla-Mendoza J.R., Rodriguez-Paez, Lorena, Figueroa-Gonzalez, Gabriela, Reyes-Hernández O.D.
Publicada:
1 ene 2022
Resumen:
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 UBE2L3 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 UBE2L3 and CYP1A1. In addition, patients’ samples were used to determine the mRNA levels of UBE2L3 and CYP1A1 genes. We found that I3C promotes the activation of AhR and decreases cell proliferation, possibly through UBE2L3 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. © 2022 by the authors.
Filiaciones:
Arellano-Gutiérrez C.V.:
Laboratorio de Bioquímica Farmacológica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de Mexico, 11340, Mexico
Quintas-Granados L.I.:
Unidad de Estudios Superiores Tultitlán, Universidad Mexiquense del Bicentenario, Estado de Mexico, 54910, Mexico
Cortes, Hernan:
Laboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México, 14389, Mexico
Del Carmen M.G.:
Facultad de Medicina, Universidad Veracruzana, Ciudad Mendoza, 94740, Mexico
Leyva-Gomez, Gerardo:
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
Bustamante-Montes L.P.:
Decanatura Ciencias de la Salud, Universidad Autónoma de Guadalajara, Guadalajara, 44670, Mexico
Rodriguez-Morales, Miguel:
Licenciatura en Médico Cirujano-INIES CUI, Ixtlahuaca Jiquipilco, San Pedro, Ixtlahuaca de Rayón, 50740, Mexico
Lopez-Reyes, Israel:
Colegio de Ciencias y Humanidades, Plantel Cuautepec, Universidad Autónoma de la Ciudad de México, Ciudad de México, 6720, Mexico
Padilla-Mendoza J.R.:
Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados (CINVESTAV-IPN), Ciudad de México, 07360, Mexico
Rodriguez-Paez, Lorena:
Laboratorio de Bioquímica Farmacológica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de Mexico, 11340, Mexico
Figueroa-Gonzalez, Gabriela:
Laboratorio de Farmacogenética, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México, 09230, Mexico
Reyes-Hernández O.D.:
Laboratorio de Biología Molecular del Cáncer, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México, 09230, Mexico
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