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

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

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.841918

DOI=10.3389/fphar.2022.841918

ISSN=1663-9812

ABSTRACT=<p>Colorectal cancer (CRC) is a common clinical malignant tumor and closely related to intestinal microbiome disorders. Especially, <italic>Fusobacterium nucleatum</italic> (<italic>F. nucleatum</italic>) 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 <italic>F. nucleatum</italic> 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 <italic>Fusobacterium</italic> was higher in CRC patients. Moreover, IPM711 and IPM712 showed better anti-<italic>F. nucleatum</italic> 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-<italic>F. nucleatum</italic> activities, providing potential natural product drug candidates for microbe-targeted strategies for the treatment of CRC.</p>