Effect of Black Raspberry Extract in Inhibiting NF B Dependent Radioprotection in Human Breast Cancer Cells
Effect of Black Raspberry Extract in Inhibiting NF B Dependent Radioprotection in Human Breast Cancer Cells
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DOI：
10.1080/01635580903191494
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发表时间：
2010-01-01
影响因子：
2.9
通讯作者：
Aravindan, Natarajan
中科院分区：
文献类型：
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作者：
Madhusoodhanan, Rakhesh;Natarajan, Mohan;Aravindan, Natarajan
黑树莓提取物（RSE）已被证明可以抑制癌细胞生长并刺激细胞凋亡。此外，研究表明，RSE抑制转录调节因子，包括NF B。因此，我们研究了RSE在抑制辐射（IR）诱导的NF B介导的乳腺癌细胞辐射防护中的作用。将MCF-7细胞暴露于IR（2Gy），用RSE（0.5、1.0、2.0 μ g/ml）处理或先用RSE（1.0 μ g/ml）处理再暴露于IR，并在1、3、6、24、48和72 h后收获。用EMSA法测定NF B DNA结合活性，用免疫印迹法测定磷酸化I B。采用QPCR和免疫印迹法检测IAP 1、IAP 2、XIAP和Survivin的表达。使用MTT测定法测量细胞存活，使用Caspase-3/7活性测量细胞死亡。观察RSE对IR所致MnSOD、TNF、IL-1及MnSOD活性的影响。RSE呈剂量依赖性抑制NF B活性。此外，RSE抑制IR诱导的NF B的持续激活，NF B调节IAP 1、IAP 2、XIAP和生存素。此外，RSE抑制IR诱导的TNF、IL-1和MnSOD水平及MnSOD活性。RSE抑制细胞存活并增强细胞死亡。这些结果表明，RSE可能作为一个有效的放射增敏剂，通过克服NF B介导的辐射保护在人乳腺癌细胞的影响。
Black raspberry extracts (RSE) have been shown to inhibit cancer cell growth and stimulate apoptosis. Also, studies have demonstrated that RSE inhibits transcriptional regulators including NF B. Accordingly, we investigated the effect of RSE in inhibiting radiation (IR) induced NF B mediated radioprotection in breast adenocarcinoma cells. MCF-7 cells were exposed to IR (2Gy), treated with RSE (0.5, 1.0, 2.0 g/ml) or treated with RSE (1.0 g/ml) followed by IR exposure, and harvested after 1, 3, 6, 24, 48, and 72 h. NF B DNA-binding activity was measured by EMSA and phosphorylated I B by immunoblotting. Expression of IAP1, IAP2, XIAP and survivin were measured by QPCR and immunoblotting. Cell survival was measured using MTT assay and cell death using Caspase-3/7 activity. Effect of RSE on IR induced MnSOD, TNF, IL-1 and MnSOD activity was also determined. RSE inhibited NF B activity in a dose-dependent manner. Also, RSE inhibited IR-induced sustained activation of NF B, and NF B regulated IAP1, IAP2, XIAP, and survivin. In addition, RSE inhibited IR-induced TNF, IL-1, and MnSOD levels and MnSOD activity. RSE suppressed cell survival and enhanced cell death. These results suggest that RSE may act as a potent radiosensitizer by overcoming the effects of NF B mediated radioprotection in human breast cancer cells.