Tannic Acid, A Hydrolysable Tannin, Prevents Transforming Growth Factor-β-Induced Epithelial-Mesenchymal Transition to Counteract Colorectal Tumor Growth

Cells. 2022 Nov 17;11(22):3645. doi: 10.3390/cells11223645.

Abstract

Despite the medico-surgical progress that has been made in the management of patients with colorectal cancer (CRC), the prognosis at five years remains poor. This resistance of cancer cells partly results from their phenotypic characteristics in connection with the epithelial-mesenchymal transition (EMT). In the present study, we have explored the ability of a polyphenol, tannic acid (TA), to counteract CRC cell proliferation and invasion through an action on the EMT. We highlight that TA decreases human SW480 and SW620 CRC cell and murine CT26 CRC cell viability, and TA inhibits their adhesion in the presence of important factors comprising the extracellular matrix, particularly in the presence of collagen type I and IV, and fibronectin. Moreover, these properties were associated with TA's ability to disrupt CRC cell migration and invasion, which are induced by transforming growth factor-β (TGF-β), as evidence in the video microscopy experiments showing that TA blocks the TGF-β1-induced migration of SW480 and CT26 cells. At the molecular level, TA promotes a reversal of the epithelial-mesenchymal transition by repressing the mesenchymal markers (i.e., Slug, Snail, ZEB1, and N-cadherin) and re-expressing the epithelial markers (i.e., E-cadherin and β-catenin). These effects could result from a disruption of the non-canonical signaling pathway that is induced by TGF-β1, where TA strongly decreases the phosphorylation of extracellular-signal regulated kinase ERK1/2, P38 and the AKT proteins that are well known to contribute to the EMT, the cell motility, and the acquisition of invasive properties by tumor cells. Very interestingly, a preclinical study of mice with subcutaneous murine tumor colon CT26 cells has shown that TA was able to significantly delay the growth of tumors without hepato- and nephrotoxicities.

Keywords: EMT; chemoprevention; colon cancer; polyphenol; tannic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins
  • Colorectal Neoplasms* / drug therapy
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Hydrolyzable Tannins
  • Mice
  • Tannins / pharmacology
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1
  • Transforming Growth Factors

Substances

  • Transforming Growth Factor beta
  • Tannins
  • Transforming Growth Factor beta1
  • Hydrolyzable Tannins
  • Cadherins
  • Transforming Growth Factors

Grant support

This work was supported by a French Government grant managed by the French National Research Agency under the program “Investissements d’Avenir”, reference ANR-11-LABX-0021, and was supported by grants from the “Conseil Régional de Bourgogne” and the “Fonds Européen de Développement Régional” (FEDER). The authors acknowledge the Tunisian Higher Education and Scientific Research Ministry for the financial support of this study.