Melatonin sensitizes human breast cancer cells to ionizing radiation by downregulating proteins involved in double-strand DNA break repair
Melatonin sensitizes human breast cancer cells to ionizing radiation by downregulating proteins involved in double-strand DNA break repair
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DOI：
10.1111/jpi.12205
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发表时间：
2015-03-01
影响因子：
10.3
通讯作者：
Cos, Samuel
中科院分区：
文献类型：
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作者：
Alonso-Gonzalez, Carolina;Gonzalez, Alicia;Cos, Samuel
放射和辅助内分泌治疗目前被认为是乳腺癌手术后的标准治疗选择。褪黑激素对人乳腺癌细胞具有抑瘤作用。在目前的研究中，我们研究了放疗和褪黑激素对人乳腺癌细胞的影响。褪黑激素（1 mM，10 μ M和1 nM）显着抑制MCF-7细胞的增殖。单独辐射以剂量依赖性方式抑制MCF-7细胞增殖。乳腺癌细胞与褪黑素辐射前1周的预处理导致MCF-7细胞增殖显着更大的下降相比，单独辐射。与单纯照射相比，照射前褪黑素预处理也减少了G（2）-M期阻滞，G（0）-G（1）期细胞百分比较高，S期细胞百分比较低。辐射单独减少RAD51和DNA蛋白激酶（PKcs）mRNA的表达，两个主要的蛋白质参与双链DNA断裂修复。与单独辐射相比，在辐射前用褪黑素处理7天导致RAD 51和DNA-PKcs mRNA表达的显著更大的降低。我们的研究结果表明，褪黑激素辐射前预处理敏感的乳腺癌细胞的电离辐射的影响，通过减少细胞增殖，诱导细胞周期阻滞和下调蛋白参与双链DNA断裂修复。这些发现可能对设计使用褪黑激素和放射治疗的临床试验有影响。
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 mu M 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 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 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.