La melatonina como modulador de los cambios moleculares inducidos por la radioterapia y la quimioterapia en el cáncer de mama

Abstract

Breast cancer, one of the most common neoplasms in women worldwide, is due to alterations in the DNA of the mammary epithelial cells. These mutations cause changes in the gene expression and trigger uncontrolled and autonomous multiplication of these cells. This proliferation forms a growing tumor that can invade adjacent tissues but also tissues away from the primary focus by dissemination of those cells through blood or lymph leading to metastasis. Conventional therapies such as radiotherapy (localized treatment that uses high-energy rays to destroy tumor cells) or chemotherapy (systemic treatment that uses drugs to kill tumor cells, including disseminated cells) have proven to be effective in fighting cancer. However, these therapies have some drawbacks. Due to their non-specificity, they present side effects that can become very serious in tissues whose cells are in active division, such as blood cells or gastrointestinal epithelial cells. These effects are reversible but sometimes the organs are seriously damaged. Another problem derived from the reiterated use of these therapies is that some tumor cells can develop resistance, survive and proliferate again. To avoid this, it is recommended to perform the sessions in cycles and to alternate different compounds, especially if the tumor reappears. The third problem is that these therapies cause changes in the proteomics of the cells. They may be altering the levels of genes and proteins related to cancer, favouring the malignancy of the cells. Because of this, it is essential to know the changes in gene expression and proteomics that cause these therapies and find some way to counteract those that are not desirable. In this work, we study the modifications caused by radiotherapy and two chemotherapy agents commonly used in clinical in breast cancer patients, on the MCF-7 cell line, cells derived from human breast adeno-carcinoma that over-express the estrogen receptor alpha. Additionally, we check the ability of melatonin to modulate these changes in a potentially beneficial way. The pineal hormone acts as an oncostatic agent that reduces the growth and development of various types of tumors, especially estrogen-dependent mammary tumors, mainly due to its anti-estrogenic properties (SERM and SEEM) so it could be considered as an excellent adjuvant for conventional therapies.