Frontiers in Pharmacology (Mar 2022)

Vanillin Derivatives Reverse Fusobacterium nucleatum-Induced Proliferation and Migration of Colorectal Cancer Through E-Cadherin/β-Catenin Pathway

  • Zhongkun Zhou,
  • Yiqing Wang,
  • Rui Ji,
  • Dekui Zhang,
  • Chi Ma,
  • Wantong Ma,
  • Yunhao Ma,
  • Xinrong Jiang,
  • Kangjia Du,
  • Rentao Zhang,
  • Peng Chen

DOI
https://doi.org/10.3389/fphar.2022.841918
Journal volume & issue
Vol. 13

Abstract

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Colorectal cancer (CRC) is a common clinical malignant tumor and closely related to intestinal microbiome disorders. Especially, Fusobacterium nucleatum (F. nucleatum) is one of the most prevalent pathogens in CRC. However, its change in CRC patients of Northwest China, an area with a high incidence of gastrointestinal tumors, is unclear, and therapeutic strategies targeting F. nucleatum remain unresolved. Here, fecal samples of healthy people and CRC patients were studied using 16S rRNA sequencing to explore microbial community alterations. Additionally, vanillin derivate (IPM711 and IPM712) intervention by coculture with CRC cells and potential mechanism were investigated. Results showed that intestinal microbial homeostasis was gradually dysregulated, and the abundance of Fusobacterium was higher in CRC patients. Moreover, IPM711 and IPM712 showed better anti-F. nucleatum activity than vanillin by increasing cell membrane permeability and destroying bacterial integrity. In addition, IPM711 and IPM712 could downregulate the expression of E-cadherin and β-catenin, thus, suppressing the migration of HCT116. Collectively, IPM711 and IPM712 have both anticolorectal cancer and anti-F. nucleatum activities, providing potential natural product drug candidates for microbe-targeted strategies for the treatment of CRC.

Keywords