Aromatic-turmerone attenuates invasion and expression of MMP-9 and COX-2 through inhibition of NF-?B activation in TPA-induced breast cancer cells
Aromatic-turmerone attenuates invasion and expression of MMP-9 and COX-2 through inhibition of NF-?B activation in TPA-induced breast cancer cells
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DOI：
10.1002/jcb.24238
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发表时间：
2012-12-01
影响因子：
4
通讯作者：
Lee, Sang-Joon
中科院分区：
文献类型：
--
作者：
Park, Sun Young;Kim, Young Hun;Lee, Sang-Joon
最近的证据表明，乳腺癌是女性最常见的恶性肿瘤之一，原发癌部位的转移是主要的死亡原因。香料姜黄酮存在于姜黄中，是一种常见的药物和食品。在本研究中，我们观察了姜黄酮对12-O-十四酰佛波醇-13-乙酸酯(TPA)诱导的乳腺癌细胞基质金属蛋白酶(MMP9)和环氧合酶-2(COX-2)表达和活性水平的抑制作用。我们的数据表明，在非细胞毒性浓度下，姜黄酮处理显著抑制了酶的活性以及基质金属蛋白酶-9和环氧合酶-2的表达。而金属蛋白酶组织抑制因子(TIMP)-1、TIMP-2、MMP2和COX-1在Ar-姜黄酮作用下的表达无明显变化。我们发现，姜黄酮抑制核因子-β的激活，但不影响AP-1的激活。此外，芯片分析显示，在体内，AR-姜黄酮显著抑制了核因子-β与基质金属蛋白酶-9和环氧合酶-2启动子的结合活性。我们的数据显示，Ar-姜黄酮降低了PI3K/Akt和ERK1/2信号的磷酸化，而不影响JNK或p38MAPK的磷酸化。因此，将PI3K/Akt和ERK1/2 siRNAs导入乳腺癌细胞，可显著降低TPA诱导的基质金属蛋白酶-9和环氧合酶-2的表达。这些结果提示，Ar-姜黄酮通过阻断人乳腺癌细胞中的NF-β、PI3K/Akt和ERK1/2信号转导通路，抑制TPA诱导的人乳腺癌细胞中MMP9和COX-2的表达上调。此外，Ar-姜黄酮显著抑制TPA诱导的人乳腺癌细胞的侵袭、迁移和集落形成。J.细胞。生物化学。2012年，113：36533662。(C)2012年威利期刊公司。
Recent evidence suggests that breast cancer is one of the most common forms of malignancy in females, and metastasis from the primary cancer site is the main cause of death. Aromatic (ar)-turmerone is present in Curcuma longa and is a common remedy and food. In the present study, we investigated the inhibitory effects of ar-turmerone on expression and enzymatic activity levels of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase (MMP)-9 and cyclooxygenaase-2 (COX-2) in breast cancer cells. Our data indicated that ar-turmerone treatment significantly inhibited enzymatic activity and expression of MMP-9 and COX-2 at non-cytotoxic concentrations. However, the expression of tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, MMP-2, and COX-1 did not change upon ar-turmerone treatment. We found that ar-turmerone inhibited the activation of NF-?B, whereas it did not affect AP-1 activation. Moreover, The ChIP assay revealed that in vivo binding activities of NF-?B to the MMP-9 and COX-2 promoter were significantly inhibited by ar-turmerone. Our data showed that ar-turmerone reduced the phosphorylation of PI3K/Akt and ERK1/2 signaling, whereas it did not affect phosphorylation of JNK or p38 MAPK. Thus, transfection of breast cancer cells with PI3K/Akt and ERK1/2 siRNAs significantly decreased TPA-induced MMP-9 and COX-2 expression. These results suggest that ar-turmerone suppressed the TPA-induced up-regulation of MMP-9 and COX-2 expression by blocking NF-?B, PI3K/Akt, and ERK1/2 signaling in human breast cancer cells. Furthermore, ar-turmerone significantly inhibited TPA-induced invasion, migration, and colony formation in human breast cancer cells. J. Cell. Biochem. 113: 36533662, 2012. (C) 2012 Wiley Periodicals, Inc.