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.

Retracted: HDAC1 inhibition by melatonin leads to suppression of lung adenocarcinoma cells via induction of oxidative stress and activation of apoptotic pathways

“…The second reason is the difference in the administration time. In a previous study , incubation with melatonin (1 m m , 10 μ m , and 1 n m ) significantly inhibited the proliferation of human breast cancer cells at 3 and 6 days; however, in the current study, the experimental cycle was only 2 days. The final reason is the difference in signaling pathways.…”

Melatonin suppresses activation of hepatic stellate cells through RORα‐mediated inhibition of 5‐lipoxygenase

“…Using culture‐activated primary rat HSC, we show in this study that melatonin suppresses HSC proliferation and activation directly. The antiproliferative action of melatonin has been intensively studied for cancer cells, in particular that of the colon , liver , breast , ovary , prostate , and pancreas . There is no universal mechanism that controls the oncostatic function of melatonin.…”

Melatonin, an inhibitory agent in breast cancer

“…It has been demonstrated that breast cancer patient with RAD51, a key player in homologous recombination and DNA repair system overexpression are more prone to resist against radiotherapy. Noteworthy, it was observed that melatonin administration for these subset of patients sensitized them to radiotherapy by downregulation of RAD51 [79].…”