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Article Open Access

Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression‑independent manner in HPV‑positive human cervical cancer‑derived cells

  • Authors:
    • Aldo F. Clemente‑Soto
    • Enrique Salas‑Vidal
    • Cesar Milan‑Pacheco
    • Jessica Nayelli Sánchez‑Carranza
    • Oscar Peralta‑Zaragoza
    • Leticia González‑Maya
  • View Affiliations / Copyright

    Affiliations: Faculty of Pharmacy, Autonomous University of Morelos State (UAEM), Cuernavaca, Morelos CP 62209, México, Department of Developmental Genetics and Molecular Physiology, National Autonomous University of Mexico, Cuernavaca, Morelos, CP 62210, México, Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Cuernavaca, Morelos, CP 62100, México
    Copyright: © Clemente‑Soto et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2097-2106
    |
    Published online on: January 11, 2019
       https://doi.org/10.3892/mmr.2019.9850
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Abstract

Cervical cancer is the second most common cancer in women worldwide. Human papillomavirus (HPV) infection appears to be a necessary factor in the development of almost all cases (>95%) of cervical cancer. HPV E6 induces a change of control of p53 stabilization from Hdm2 to E6/E6AP in HPV‑infected cells. It is well known that the LxxLL motif of cellular ubiquitin ligase E6AP binds to the pocket of E6 and causes a conformational change to enable E6 to bind p53 competently. In the ternary complex E6/E6AP/p53, p53 is polyubiquitinated by E6AP and subsequently degraded by a proteasome. Therefore, these cells are deficient in the processes regulated by p53, including apoptosis, damaged DNA repair, and the cell cycle. In the present study, it was demonstrated that quercetin induced G2 phase cell cycle arrest and apoptosis in both HeLa and SiHa cells, accompanied by an increase of p53 and its nuclear signal. It was also observed that quercetin increased the level of the p21 transcript and the pro‑apoptotic Bax protein, which are two p53‑downstream effectors. However, quercetin did not alter the expression of the HPV E6 protein in cervical cancer cells; therefore, the increase in p53 occurred in an E6 expression‑independent manner. Furthermore, molecular docking demonstrated that quercetin binds stably in the central pocket of E6, the binding site of E6AP. These data suggest that quercetin increases the nuclear localization of p53 by interrupting E6/E6AP complex formation in cervical cancer cells.
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Copy and paste a formatted citation
Spandidos Publications style
Clemente‑Soto AF, Salas‑Vidal E, Milan‑Pacheco C, Sánchez‑Carranza JN, Peralta‑Zaragoza O and González‑Maya L: Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression‑independent manner in HPV‑positive human cervical cancer‑derived cells. Mol Med Rep 19: 2097-2106, 2019.
APA
Clemente‑Soto, A.F., Salas‑Vidal, E., Milan‑Pacheco, C., Sánchez‑Carranza, J.N., Peralta‑Zaragoza, O., & González‑Maya, L. (2019). Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression‑independent manner in HPV‑positive human cervical cancer‑derived cells. Molecular Medicine Reports, 19, 2097-2106. https://doi.org/10.3892/mmr.2019.9850
MLA
Clemente‑Soto, A. F., Salas‑Vidal, E., Milan‑Pacheco, C., Sánchez‑Carranza, J. N., Peralta‑Zaragoza, O., González‑Maya, L."Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression‑independent manner in HPV‑positive human cervical cancer‑derived cells". Molecular Medicine Reports 19.3 (2019): 2097-2106.
Chicago
Clemente‑Soto, A. F., Salas‑Vidal, E., Milan‑Pacheco, C., Sánchez‑Carranza, J. N., Peralta‑Zaragoza, O., González‑Maya, L."Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression‑independent manner in HPV‑positive human cervical cancer‑derived cells". Molecular Medicine Reports 19, no. 3 (2019): 2097-2106. https://doi.org/10.3892/mmr.2019.9850
Copy and paste a formatted citation
x
Spandidos Publications style
Clemente‑Soto AF, Salas‑Vidal E, Milan‑Pacheco C, Sánchez‑Carranza JN, Peralta‑Zaragoza O and González‑Maya L: Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression‑independent manner in HPV‑positive human cervical cancer‑derived cells. Mol Med Rep 19: 2097-2106, 2019.
APA
Clemente‑Soto, A.F., Salas‑Vidal, E., Milan‑Pacheco, C., Sánchez‑Carranza, J.N., Peralta‑Zaragoza, O., & González‑Maya, L. (2019). Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression‑independent manner in HPV‑positive human cervical cancer‑derived cells. Molecular Medicine Reports, 19, 2097-2106. https://doi.org/10.3892/mmr.2019.9850
MLA
Clemente‑Soto, A. F., Salas‑Vidal, E., Milan‑Pacheco, C., Sánchez‑Carranza, J. N., Peralta‑Zaragoza, O., González‑Maya, L."Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression‑independent manner in HPV‑positive human cervical cancer‑derived cells". Molecular Medicine Reports 19.3 (2019): 2097-2106.
Chicago
Clemente‑Soto, A. F., Salas‑Vidal, E., Milan‑Pacheco, C., Sánchez‑Carranza, J. N., Peralta‑Zaragoza, O., González‑Maya, L."Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression‑independent manner in HPV‑positive human cervical cancer‑derived cells". Molecular Medicine Reports 19, no. 3 (2019): 2097-2106. https://doi.org/10.3892/mmr.2019.9850
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