title: Melatonin sensitizes human breast cancer cells to ionizing radiation by downregulating proteins involved in double-strand DNA break repair.
abstract: Radiation and adjuvant endocrine therapy are nowadays considered a standard treatment option after surgery in breast cancer. Melatonin exerts oncostatic actions on human breast cancer cells. In the current study, we investigated the effects of a combination of radiotherapy and melatonin on human breast cancer cells. Melatonin (1 mm, 10 μm and 1 nm) significantly inhibited the proliferation of MCF-7 cells. Radiation alone inhibited the MCF-7 cell proliferation in a dose-dependent manner. Pretreatment of breast cancer cells with melatonin 1 wk before radiation led to a significantly greater decrease of MCF-7 cell proliferation compared with radiation alone. Melatonin pretreatment before radiation also decreased G2 -M phase arrest compared with irradiation alone, with a higher percentage of cells in the G0 -G1 phase and a lower percentage of cells in S phase. Radiation alone diminished RAD51 and DNA-protein kinase (PKcs) mRNA expression, two main proteins involved in double-strand DNA break repair. Treatment with melatonin for 7 days before radiation led to a significantly greater decrease in RAD51 and DNA-PKcs mRNA expression compared with radiation alone. Our findings suggest that melatonin pretreatment before radiation sensitizes breast cancer cells to the ionizing effects of radiation by decreasing cell proliferation, inducing cell cycle arrest and downregulating proteins involved in double-strand DNA break repair. These findings may have implications for designing clinical trials using melatonin and radiotherapy.
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, University of Cantabria and Instituto de Investigación Valdecilla (IDIVAL), Santander, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Alonso-González
authors.forename: Alicia
authors.initials: A
authors.lastname: González
authors.forename: Carlos
authors.initials: C
authors.lastname: Martínez-Campa
authors.forename: José
authors.initials: J
authors.lastname: Gómez-Arozamena
authors.forename: Samuel
authors.initials: S
authors.lastname: Cos
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008550:Melatonin / Q000494:pharmacology*; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing
chemical_list: D051135:Rad51 Recombinase; D008550:Melatonin
keywords: DNA-PKcs; MCF-7 cells; RAD51; breast cancer; melatonin; pineal gland; radiation