Issue 11, 2018

Tannic acid directly targets pyruvate kinase isoenzyme M2 to attenuate colon cancer cell proliferation

Abstract

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.

Graphical abstract: Tannic acid directly targets pyruvate kinase isoenzyme M2 to attenuate colon cancer cell proliferation

Supplementary files

Article information

Article type
Paper
Submitted
11 Jun 2018
Accepted
28 Aug 2018
First published
06 Sep 2018

Food Funct., 2018,9, 5547-5559

Tannic acid directly targets pyruvate kinase isoenzyme M2 to attenuate colon cancer cell proliferation

P. Yang, G. Ding, W. Liu, R. Fu, A. Sajid and Z. Li, Food Funct., 2018, 9, 5547 DOI: 10.1039/C8FO01161C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements