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Melatonin sensitizes human breast cancer cells to ionizing radiation by downregulating proteins involved in double‐strand DNA break repair
Author(s) -
AlonsoGonzález Carolina,
González Alicia,
MartínezCampa Carlos,
GómezArozamena José,
Cos Samuel
Publication year - 2015
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12205
Subject(s) - melatonin , breast cancer , cell cycle , cancer research , cell growth , dna repair , radiation therapy , apoptosis , cancer cell , ionizing radiation , biology , endocrinology , cell cycle checkpoint , cancer , medicine , dna damage , irradiation , dna , biochemistry , physics , nuclear physics
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 m m , 10 μ m and 1 n m ) 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 G 2 ‐M phase arrest compared with irradiation alone, with a higher percentage of cells in the G 0 ‐G 1 phase and a lower percentage of cells in S phase. Radiation alone diminished RAD 51 and DNA ‐protein kinase ( PK cs) 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 RAD 51 and DNA − PK cs 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.