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

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

doi:10.3892/ol.2018.9758

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
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Affiliations: Faculty of Medicine of São José do Rio Preto (FAMERP), Department of Molecular Biology, São José do Rio Preto, SP 15090‑000, Brazil, Laboratory of Cancer Molecular Investigation (LIMC), Department of Molecular Biology, Faculty of Medicine of São José do Rio Preto (FAMERP), São José do Rio Preto, SP 15090‑000, Brazil
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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