Melatonin enhances the apoptotic effects and modulates 
the changes in gene expression induced by docetaxel in MCF‑7 human breast cancer cells

Alonso-González,Carolina; Menéndez-Menéndez,Javier; González-González,Alicia; González,Alicia; Cos,Samuel; Martínez-Campa,Carlos

doi:10.3892/ijo.2017.4213

Melatonin enhances the apoptotic effects and modulates the changes in gene expression induced by docetaxel in MCF‑7 human breast cancer cells

Authors:
- Carolina Alonso-González
- Javier Menéndez-Menéndez
- Alicia González-González
- Alicia González
- Samuel Cos
- Carlos Martínez-Campa
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Affiliations: Department of Physiology and Pharmacology, School of Medicine, University of Cantabria and Valdecilla Research Institute (IDIVAL), ES-39011 Santander, Spain
Published online on: November 28, 2017 https://doi.org/10.3892/ijo.2017.4213
Pages: 560-570

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Abstract

Results from clinical trials and multiple in vivo and in vitro studies point to melatonin as a promising adjuvant molecule with many beneficial effects when concomitantly administered with chemotherapy. Melatonin palliates side‑effects and enhances the efficacy of chemotherapeutic agents. However, the mechanisms through which melatonin regulates molecular changes induced by chemotherapeutic agents remain largely unknown. In this study, we demonstrated that melatonin enhanced the anti-proliferative and apoptotic responses to low doses of docetaxel in breast cancer cells. Importantly, these effects were more potent when melatonin was added prior to docetaxel. Treatment with 1 µM docetaxel (equivalent to the therapeutic dosage) induced changes in gene expression profiles and melatonin modulated these changes. Specifically, docetaxel downregulated TP53, cyclin-dependent kinase inhibitor 1A (CDKN1A) and cadherin 13 (CDH13), and upregulated mucin 1 (MUC1), GATA binding protein 3 (GATA3) and c-MYC, whereas melatonin counteracted these effects. Melatonin further stimulated the expression of the pro-apoptotic BAD and BAX genes, and enhanced the inhibition of the anti-apoptotic gene BCL-2 induced by docetaxel. The findings of this study suggest that melatonin is a molecule with potential for use as an adjuvant in cancer chemotherapy, which may have implications for designing clinical trials using chemotherapeutic drugs in combination with melatonin.

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