Tannic acid directly targets pyruvate kinase isoenzyme M2 to attenuate colon cancer cell proliferation†,Food & Function

当前位置： X-MOL 学术 › Food Funct. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Tannic acid directly targets pyruvate kinase isoenzyme M2 to attenuate colon cancer cell proliferation†
Food & Function ( IF 5.1 ) Pub Date : 2018-09-06 00:00:00 , DOI: 10.1039/c8fo01161c
Peng Yang _{1,

2,

3,

4,

5} , Guo-Bin Ding _{1,

2,

3,

4,

5} , Wen Liu _{1,

2,

3,

4,

5} , Rong Fu _{1,

2,

3,

4,

5} , Amin Sajid _{1,

2,

3,

4,

5} , Zhuoyu Li _{1,

2,

3,

4,

5}

Affiliation

Tannic acid (TA), a naturally occurring polyphenolic acid that is primarily found in grapes and green tea, exhibits potent antioxidant and anticarcinogenic characteristics. However, the underlying molecular mechanisms and targets of TA, which are responsible for cancer prevention, remain elusive. In the present study, we used TA-functionalized magnetite nanoparticles to identify pyruvate kinase isoenzyme M2 (PKM2) as the direct target of TA. We report that TA selectively inhibits the pyruvate kinase activity of PKM2, rather than protein kinase activity and PKM2 expression, to suppress colorectal cancer (CRC) cell proliferation. Furthermore, we had discovered that lysine residue 433 (K433) is a selective druggable site. Through direct binding to lysine residue 433, TA triggers the dissociation of PKM2 tetramers and further blocks the metabolic activity of PKM2. Notably, TA has no effect on PKM1 activity as TA does not bind to it. Taken together, these findings show that TA is worthy of consideration as a promising PKM2 inhibitor for the prevention of CRC.

中文翻译：

单宁酸直接靶向丙酮酸激酶同工酶M2以减弱结肠癌细胞的增殖†

单宁酸（TA）是一种天然存在的多酚酸，主要存在于葡萄和绿茶中，具有强大的抗氧化和抗癌特性。然而，负责癌症预防的潜在的分子机制和靶标仍然难以捉摸。在本研究中，我们使用TA功能化的磁铁矿纳米颗粒来确定丙酮酸激酶同工酶M2（PKM2）作为TA的直接靶标。我们报告说，TA选择性抑制PKM2的丙酮酸激酶活性，而不是蛋白激酶活性和PKM2的表达，以抑制结直肠癌（CRC）细胞增殖。此外，我们发现赖氨酸残基433（K433）是一个选择性的可成药位点。通过直接结合赖氨酸残基433，TA触发PKM2四聚体的解离，并进一步阻断PKM2的代谢活性。值得注意的是，TA对PKM1活性没有影响，因为TA不与其结合。综上所述，这些发现表明TA值得作为有前途的PKM2抑制剂来预防CRC。

更新日期：2018-09-06

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11