Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells.

Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells.
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DOI:
10.1038/sj.bjc.6604521
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发表时间:
2008-08-19
影响因子:
8.8
通讯作者:
Shibata, T.
Shibata, T.
中科院分区:
医学1区
文献类型:
--
作者:
Kato, K.;Long, N. K.;Makita, H.;Toida, M.;Yamashita, T.;Hatakeyama, D.;Hara, A.;Mori, H.;Shibata, T.

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RECK基因是一种新的肿瘤抑制基因,它能负性调节基质金属蛋白酶(MMPs),抑制肿瘤的侵袭、血管生成和转移。在本研究中,我们研究了表没食子儿茶素-3-没食子酸酯(EGCG),绿色茶中的主要多酚,对口腔鳞状细胞癌细胞系中RECK基因甲基化状态和癌症侵袭的影响。我们的研究结果表明,用EGCG处理口腔癌细胞部分逆转了RECK基因的高甲基化状态,并显着提高了RECK mRNA的表达水平。用EGCG处理后,在这些细胞中也观察到MMP-2和MMP-9水平的抑制。有趣的是,在三维胶原浸润模型中,EGCG通过减少浸润灶的数量(P<0.0001)以及浸润深度(P<0.005)显著抑制癌细胞的浸润能力。虽然需要进一步的研究来评估RECK对MMP抑制侵袭行为的贡献程度,但这些结果支持以下结论:EGCG通过多种机制在抑制细胞侵袭中起关键作用,可能是通过对MMP抑制剂如RECK的去甲基化作用。
RECK is a novel tumour suppressor gene that negatively regulates matrix metalloproteinases (MMPs) and inhibits tumour invasion, angiogenesis and metastasis. In the present study, we investigated the effects of epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, on the methylation status of the RECK gene and cancer invasion in oral squamous cell carcinoma cell lines. Our results showed that treatment of oral cancer cells with EGCG partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression level of RECK mRNA. Inhibition of MMP-2 and MMP-9 levels was also observed in these cells after treatment with EGCG. Interestingly, EGCG significantly suppressed cancer cell-invasive ability by decreasing the number of invasive foci (P<0.0001) as well as invasion depth (P<0.005) in three-dimensional collagen invasion model. Although further investigation is required to assess the extent of contribution of RECK on MMPs to the suppression of invasive behaviour, these results support the conclusion that EGCG plays a key role in suppressing cell invasion through multiple mechanisms, possibly by demethylation effect on MMP inhibitors such as RECK.
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