Bio-IT Fusion Technology Research Institute, Pusan National University, Busan 609-735, Republic of Korea.
J Cell Biochem. 2012 Dec;113(12):3653-62. doi: 10.1002/jcb.24238.
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-κB, whereas it did not affect AP-1 activation. Moreover, The ChIP assay revealed that in vivo binding activities of NF-κB 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-κB, 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.
最近的证据表明，乳腺癌是女性最常见的恶性肿瘤之一，而原发性癌症部位的转移是导致死亡的主要原因。芳基（ar）-姜黄素存在于姜黄中，是一种常见的药物和食品。在本研究中，我们研究了 ar-姜黄素对乳腺癌细胞中 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的基质金属蛋白酶（MMP）-9 和环氧化酶-2（COX-2）表达和酶活性水平的抑制作用。我们的数据表明，ar-姜黄素在非细胞毒性浓度下显著抑制 MMP-9 和 COX-2 的酶活性和表达。然而，ar-姜黄素处理后组织金属蛋白酶抑制剂（TIMP）-1、TIMP-2、MMP-2 和 COX-1 的表达没有改变。我们发现 ar-姜黄素抑制 NF-κB 的激活，但不影响 AP-1 的激活。此外，ChIP 分析显示，ar-姜黄素显著抑制 NF-κB 与 MMP-9 和 COX-2 启动子的体内结合活性。我们的数据表明，ar-姜黄素降低了 PI3K/Akt 和 ERK1/2 信号的磷酸化，而不影响 JNK 或 p38 MAPK 的磷酸化。因此，用 PI3K/Akt 和 ERK1/2 siRNA 转染乳腺癌细胞可显著降低 TPA 诱导的 MMP-9 和 COX-2 表达。这些结果表明，ar-姜黄素通过阻断 NF-κB、PI3K/Akt 和 ERK1/2 信号通路，抑制 TPA 诱导的 MMP-9 和 COX-2 表达，从而抑制人乳腺癌细胞的表达。此外，ar-姜黄素显著抑制 TPA 诱导的人乳腺癌细胞侵袭、迁移和集落形成。
