TY - JOUR
T1 - Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest
AU - Arellano-Gutiérrez, Claudia Vanessa
AU - Quintas-Granados, Laura Itzel
AU - Cortés, Hernán
AU - Del Carmen, Manuel González
AU - Leyva-Gómez, Gerardo
AU - Bustamante-Montes, Lilia Patricia
AU - Rodríguez-Morales, Miguel
AU - López-Reyes, Israel
AU - Padilla-Mendoza, Juan Ramón
AU - Rodríguez-Páez, Lorena
AU - Figueroa-González, Gabriela
AU - Reyes-Hernández, Octavio Daniel
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
KW - UBE2L3
KW - cellular proliferation
KW - cervical cancer
KW - indole-3-carbinol
UR - http://www.scopus.com/inward/record.url?scp=85130241910&partnerID=8YFLogxK
U2 - 10.3390/cimb44050139
DO - 10.3390/cimb44050139
M3 - Artículo
C2 - 35678668
AN - SCOPUS:85130241910
SN - 1467-3037
VL - 44
JO - Current Issues in Molecular Biology
JF - Current Issues in Molecular Biology
IS - 5
M1 - 2054
ER -