Involvement of 67-kDa laminin receptor-mediated myosin phosphatase activation in antiproliferative effect of epigallocatechin-3-O-gallate at a physiological concentration on Caco-2 colon cancer cells
Involvement of 67-kDa laminin receptor-mediated myosin phosphatase activation in antiproliferative effect of epigallocatechin-3-O-gallate at a physiological concentration on Caco-2 colon cancer cells
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DOI：
10.1016/j.bbrc.2008.04.041
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发表时间：
2008-06-20
影响因子：
3.1
通讯作者：
Tachibana, Hirofumi
中科院分区：
文献类型：
--
作者：
Umeda, Daisuke;Yano, Satomi;Tachibana, Hirofumi
以前我们报道，67-kDa层粘连蛋白受体（67 LR）介导表没食子儿茶素-3-O-没食子酸酯（EGCG）诱导的细胞生长抑制和肌球蛋白调节轻链（MRLC）磷酸化的减少在Thr-18/Ser-19，这是重要的胞质分裂。在此，我们发现人结肠腺癌Caco-2细胞表现出较高的67 LR表达水平，并且在生理可达到的浓度（1 μ M）下，EGCG显著地使细胞聚集在G（2）/M期，而不影响Wnt信号传导组分的表达。我们还发现，肌球蛋白磷酸酶靶向亚基1（MYPT 1）磷酸化在Thr-696，抑制肌球蛋白磷酸酶和促进MRLC磷酸化，减少响应1 μ M的EGCG。通过RNA干扰敲低67 LR消除了1 μ M EGCG对细胞周期进程和MRLC和MYPT 1磷酸化的抑制作用。这些结果表明，通过67 LR，在生理浓度的EGCG可以激活肌球蛋白磷酸酶通过减少MYPT 1磷酸化，并可能参与EGCG诱导的细胞生长抑制。(C)2008年爱思唯尔公司All rights reserved.
Previously we reported that 67-kDa laminin receptor (67LR) mediates epigallocatechin-3-O-gallate (EGCG)-induced cell growth inhibition and reduction of myosin regulatory light chain (MRLC) phosphorylation at Thr-18/Ser-19, which is important for cytokinesis. Here, we found that human colon adenocarcinoma Caco-2 cells exhibited higher expression level of 67LR and EGCG at a physiologically achievable concentration (1 mu M) significantly accumulated the cells in G(2)/M phase without affecting expression of Wnt-signaling components. We also found that myosin phosphatase targeting subunit 1 (MYPT1) phosphorylation at Thr-696, which inhibits myosin phosphatase and Promotes MRLC phosphorylation, was reduced in response to 1 mu M EGCG. 67LR knockdown by RNA interference abolished the inhibitory effects of 1 mu M EGCG on cell cycle progression and the phosphorylation of MRLC and MYPT1. These results suggest that through 67LR, EGCG at a physiological concentration can activate myosin phosphatase by reducing MYPT1 phosphorylation and that may be involved in EGCG-induced cell growth inhibition. (C) 2008 Elsevier Inc. All rights reserved.