Open Access

17β‑estradiol‑induced mitochondrial dysfunction and Warburg effect in cervical cancer cells allow cell survival under metabolic stress

  • Authors:
    • Annie Riera Leal
    • Pablo César Ortiz‑Lazareno
    • Luis Felipe Jave‑Suárez
    • Adrián Ramírez De Arellano
    • Adriana Aguilar‑Lemarroy
    • Yveth Marlene Ortiz‑García
    • Carlos Alfredo Barrón‑Gallardo
    • Raúl Solís‑Martínez
    • Sonia Luquin De Anda
    • José Francisco Muñoz‑Valle
    • Ana Laura Pereira‑Suárez
  • View Affiliations

  • Published online on: November 14, 2019     https://doi.org/10.3892/ijo.2019.4912
  • Pages: 33-46
  • Copyright: © Riera Leal et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mitochondria from different types of cancer show bioenergetics and dysfunction that favor cell proliferation. The mechanistic understanding of estrogen in cervical cancer is poorly understood. Therefore, the objective of this study was to determine how 17β‑estradiol (E2) affects mitochondrial function and the Warburg effect in SiHa, HeLa and C33A cervical cancer cells. Mitochondrial compromise was evaluated measuring changes in the membrane permeability by immunofluorescence, calcium concentration, redox status, iron and ferritin reserves. Glucose consumption and lactic acid assays were used to detect the metabolic activity. Results were confirmed at molecular level by analysis of the differential gene expression using RNA sequencing. E2 modified the mitochondrial permeability and produced an alteration in the calcium signaling pathway. In HeLa and SiHa, there was a significant decrease in nitric oxide levels and lipid peroxidation, and an increase in glucose consumption and lactic acid levels when stimulated with E2. Intracellular iron or ferritin reserves were not affected by the E2 treatment. Genes differentially modulated by E2 were involved in the mitochondrial electron transport chain, oxidative phosphorylation system, glycolysis, pentose phosphate pathway and the regulation of metabolic signaling pathways. Herein, we provide evidence for a primary effect of estrogen on mitochondrial function and the Warburg effect, favoring the metabolic adaptation of the cervical cancer cell lines and their survival.
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January 2020
Volume 56 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Riera Leal, A., Ortiz‑Lazareno, P.C., Jave‑Suárez, L.F., Ramírez De Arellano, A., Aguilar‑Lemarroy, A., Ortiz‑García, Y.M. ... Pereira‑Suárez, A.L. (2020). 17β‑estradiol‑induced mitochondrial dysfunction and Warburg effect in cervical cancer cells allow cell survival under metabolic stress. International Journal of Oncology, 56, 33-46. https://doi.org/10.3892/ijo.2019.4912
MLA
Riera Leal, A., Ortiz‑Lazareno, P. C., Jave‑Suárez, L. F., Ramírez De Arellano, A., Aguilar‑Lemarroy, A., Ortiz‑García, Y. M., Barrón‑Gallardo, C. A., Solís‑Martínez, R., Luquin De Anda, S., Muñoz‑Valle, J. F., Pereira‑Suárez, A. L."17β‑estradiol‑induced mitochondrial dysfunction and Warburg effect in cervical cancer cells allow cell survival under metabolic stress". International Journal of Oncology 56.1 (2020): 33-46.
Chicago
Riera Leal, A., Ortiz‑Lazareno, P. C., Jave‑Suárez, L. F., Ramírez De Arellano, A., Aguilar‑Lemarroy, A., Ortiz‑García, Y. M., Barrón‑Gallardo, C. A., Solís‑Martínez, R., Luquin De Anda, S., Muñoz‑Valle, J. F., Pereira‑Suárez, A. L."17β‑estradiol‑induced mitochondrial dysfunction and Warburg effect in cervical cancer cells allow cell survival under metabolic stress". International Journal of Oncology 56, no. 1 (2020): 33-46. https://doi.org/10.3892/ijo.2019.4912