Modifying effects of dietary factors on (-)-epigallocatechin-3-gallate-induced pro-matrix metalloproteinase-7 production in HT-29 human colorectal cancer cells
Modifying effects of dietary factors on (-)-epigallocatechin-3-gallate-induced pro-matrix metalloproteinase-7 production in HT-29 human colorectal cancer cells
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DOI：
10.1271/bbb.70213
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发表时间：
2007-10-01
影响因子：
1.6
通讯作者：
Ohigashi, Hajime
中科院分区：
文献类型：
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作者：
Kim, Mihye;Murakami, Akira;Ohigashi, Hajime
表没食子儿茶素没食子酸酯（EGCG）是绿色茶的主要成分之一，具有化学预防作用。与此相反，我们最近报道，表没食子儿茶素没食子酸酯增强前基质金属蛋白酶（MMP）-7在HT-29人结肠癌细胞通过自发产生超氧化物。在本研究中，我们研究了膳食抗氧化剂对HT-29细胞自发和EGCG上调的proMMP-7产生的影响。异硫氰酸苄酯（BITC）、姜黄素（CUR）、没食子酸（GA）和N-乙酰基-L-半胱氨酸（NAC）降低了这种产生，而每一种单独使用对自发产生没有任何影响。在测试的培养基中，没有任何饮食因素抑制EGCG诱导的过氧化氢生成，而BITC、GA和NAC分别抑制了126%、77%和97%的EGCG增强的激活蛋白（AP）-1转录活性。虽然CUR消除了EGCG上调的MMP-7 mRNA表达，但它意外地将AP-1活性提高了502%，表明该因子可能破坏MMP-7 mRNA稳定过程。总之，我们的研究结果表明，膳食抗氧化剂通过不同的机制调节EGCG诱导的MMP-7的产生。
(-)-Epigallocatechin-3-gallate (EGCG), one of the main constituents of green tea, has been reported to function as an antioxidant with chemopreventive potential. In contrast, we have recently reported that EGCG enhanced pro-matrix metalloproteinase (MMP)-7 in HT-29 human colon cancer cells via spontaneous superoxide generation. In the present study, we examined the effects of dietary antioxidants on both spontaneous and EGCG-upregulated proMMP-7 production in HT-29 cells. Benzyl isothiocyanate (BITC), curcumin (CUR), gallic acid (GA), and N-acetyl-L-cysteine (NAC) reduced that production, while each alone did not have any effect on spontaneous production. None of the dietary factors suppressed EGCG-induced hydrogen peroxide generation in the media tested, whereas BITC, GA, and NAC inhibited the EGCG-enhanced activator protein (AP)-1 transcription activity by 126%, 77%, and 97%, respectively. Although CUR abolished the EGCG-upregulated MMP-7 mRNA expression, it unexpectedly enhanced the AP-1 activity by 502%, suggesting that this factor may disrupt the MMP-7 mRNA stabilization process. Together, our results indicate that dietary antioxidants modulate EGCG-induced MMP-7 production through different mechanisms.