Open Access

Melatonin regulates tumor aggressiveness under acidosis condition in breast cancer cell lines

  • Authors:
    • Nathália Martins Sonehara
    • Jéssica Zani Lacerda
    • Bruna Victorasso Jardim‑Perassi
    • Rubens de Paula Jr
    • Marina Gobbe Moschetta‑Pinheiro
    • Ynaiá Santos Traba Souza
    • Júlia Carolina Junqueira de Andrade
    • Debora Aparecida Pires de Campos Zuccari
  • View Affiliations

  • Published online on: November 26, 2018     https://doi.org/10.3892/ol.2018.9758
  • Pages: 1635-1645
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Abstract

Breast cancer progression is composed of multiple steps that are influenced by tumor cell adaptations to survive under acidic conditions in the tumor microenvironment. Regulation of this cell survival behavior is a promising strategy to avoid cancer development. Melatonin is a natural hormone produced and secreted by the pineal gland capable of modulating different biological pathways in cancer. Although the anti‑cancer effects of melatonin are currently widespread, its role in the acid tumor microenvironment remains poorly understood. The aim of the present study was to investigate the effect of low pH (6.7) on human breast cancer cell lines MCF‑7 and MDA‑MB‑231, and the effectiveness of melatonin in acute acidosis survival mechanisms. Cell viability was measured by a MTT assay and the protein expression of glucose transporter (GLUT)‑1, Ki‑67 and caspase‑3 was evaluated by immunocytochemical (ICC) analysis following low pH media and melatonin treatment. In both cell lines the viability was decreased after melatonin treatment (1 mM) under acidosis conditions for 24 h. ICC analysis showed a significant increase in GLUT‑1 and Ki‑67 expression at pH 6.7, and a decrease after treatment with melatonin for 12 and 24 h. The low pH media decreased the expression of caspase‑3, which was increased after melatonin treatment for 12 and 24 h. Overall, the results of the present study revealed melatonin treatment increases apoptosis, as indicated by changes in caspase‑3, and decreases proliferation, indicated by changes to Ki‑67, and GLUT‑1 protein expression under acute acidosis conditions in breast cancer cell lines.
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February-2019
Volume 17 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Sonehara NM, Lacerda JZ, Jardim‑Perassi BV, de Paula Jr R, Moschetta‑Pinheiro MG, Souza YS, de Andrade JC and Zuccari DA: Melatonin regulates tumor aggressiveness under acidosis condition in breast cancer cell lines. Oncol Lett 17: 1635-1645, 2019
APA
Sonehara, N.M., Lacerda, J.Z., Jardim‑Perassi, B.V., de Paula Jr, R., Moschetta‑Pinheiro, M.G., Souza, Y.S. ... Zuccari, D.A. (2019). Melatonin regulates tumor aggressiveness under acidosis condition in breast cancer cell lines. Oncology Letters, 17, 1635-1645. https://doi.org/10.3892/ol.2018.9758
MLA
Sonehara, N. M., Lacerda, J. Z., Jardim‑Perassi, B. V., de Paula Jr, R., Moschetta‑Pinheiro, M. G., Souza, Y. S., de Andrade, J. C., Zuccari, D. A."Melatonin regulates tumor aggressiveness under acidosis condition in breast cancer cell lines". Oncology Letters 17.2 (2019): 1635-1645.
Chicago
Sonehara, N. M., Lacerda, J. Z., Jardim‑Perassi, B. V., de Paula Jr, R., Moschetta‑Pinheiro, M. G., Souza, Y. S., de Andrade, J. C., Zuccari, D. A."Melatonin regulates tumor aggressiveness under acidosis condition in breast cancer cell lines". Oncology Letters 17, no. 2 (2019): 1635-1645. https://doi.org/10.3892/ol.2018.9758