Green tea phenolics inhibit butyrate-induced differentiation of colon cancer cells by interacting with monocarboxylate transporter 1.
Green tea phenolics inhibit butyrate-induced differentiation of colon cancer cells by interacting with monocarboxylate transporter 1.
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DOI：
10.1016/j.bbadis.2013.08.009
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Cascante M
中科院分区：
文献类型：
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作者：
Sánchez-Tena S;Vizán P;Dudeja PK;Centelles JJ;Cascante M
饮食对结直肠癌有显著影响，膳食纤维和植物性化合物都被独立证明与结肠癌风险呈负相关。丁酸盐（NaB）是膳食纤维发酵的主要产物之一，通过抑制组蛋白去乙酰化酶（hdac）诱导结肠癌细胞分化。另一方面，(−)-表儿茶素（EC）和(−)-表没食子儿茶素没食子酸酯（EGCG），绿茶中两种丰富的酚类化合物，已被证明具有抗肿瘤特性。在这项研究中，我们用结肠癌细胞系研究了NaB、EC和EGCG共处理过程中发生的细胞和分子事件。我们发现(i)多酚EC和EGCG不能诱导结肠癌细胞系分化；（ii）多酚EC和EGCG减少nab诱导的分化；（iii）多酚对NaB的作用是特异性的，因为其他药物如trichostatin A （TSA）诱导的分化在EC和EGCG处理后没有改变，（iv）与NaB的HDAC抑制活性无关。(5)多酚类物质部分降低细胞NaB；（vi）在分子水平上，多酚通过损害NaB在质膜中重新定位自身转运蛋白（单羧酸转运蛋白1，MCT1）的能力来减少细胞对NaB的摄取。我们的研究结果表明，绿茶酚类补充剂可能会降低NaB对结直肠癌的有益作用。这些有价值的信息应该有助于选择合理的设计，以更有效地预防或治疗结直肠癌的饮食驱动治疗干预措施。
Diet has a significant impact on colorectal cancer and both dietary fiber and plant-derived compounds have been independently shown to be inversely related to colon cancer risk. Butyrate (NaB), one of the principal products of dietary fiber fermentation, induces differentiation of colon cancer cell lines by inhibiting histone deacetylases (HDACs). On the other hand, (−)-epicatechin (EC) and (−)-epigallocatechin gallate (EGCG), two abundant phenolic compounds of green tea, have been shown to exhibit antitumoral properties. In this study we used colon cancer cell lines to study the cellular and molecular events that take place during co-treatment with NaB, EC and EGCG. We found that (i) polyphenols EC and EGCG fail to induce differentiation of colon adenocarcinoma cell lines; (ii) polyphenols EC and EGCG reduce NaB-induced differentiation; (iii) the effect of the polyphenols is specific for NaB, since differentiation induced by other agents, such as trichostatin A (TSA), was unaltered upon EC and EGCG treatment, and (iv) is independent of the HDAC inhibitory activity of NaB. Also, (v) polyphenols partially reduce cellular NaB; and (vi) on a molecular level, reduction of cellular NaB uptake by polyphenols is achieved by impairing the capacity of NaB to relocalize its own transporter (monocarboxylate transporter 1, MCT1) in the plasma membrane. Our findings suggest that beneficial effects of NaB on colorectal cancer may be reduced by green tea phenolic supplementation. This valuable information should be of assistance in choosing a rational design for more effective diet-driven therapeutic interventions in the prevention or treatment of colorectal cancer.