Sodium New Houttuyfonate Inhibits Cancer-Promoting Fusobacterium nucleatum (Fn) to Reduce Colorectal Cancer...

Area of Science:

• Microbiology
• Oncology
• Pharmacology

Background:

• Colorectal cancer (CRC) presents a significant global health burden.
• Fusobacterium nucleatum (Fn) is increasingly recognized for its role in CRC development, metastasis, and treatment resistance.
• Current CRC treatments lack specific antimicrobial strategies targeting associated bacteria.

Purpose of the Study:

• To investigate the antimicrobial activity of six phytochemicals against Fn.
• To evaluate the potential of anti-Fn phytochemicals in modulating Fn-associated CRC.
• To identify a specific phytochemical for potential CRC antimicrobial therapy.

Main Methods:

• Screening of six common phytochemicals for antimicrobial activity against Fn.
• Assessment of cytotoxicity of active phytochemicals on cancer and normal cells (in vitro and in vivo).
• Mechanistic studies involving Fn's FadA protein and intestinal barrier integrity.
• Evaluation of SNH efficacy in a mouse xenograft model of CRC with Fn inoculation.

Main Results:

• SNH demonstrated the highest antimicrobial activity against Fn with minimal cytotoxicity.
• SNH targets membrane-associated FadA, leading to bacterial membrane disruption.
• SNH suppressed Fn-driven inflammation, improved the intestinal barrier, and reduced Fn load in vivo.
• SNH significantly inhibited CRC progression in a mouse model.

Conclusions:

• SNH exhibits potent antimicrobial activity against Fn and possesses anti-CRC properties.
• SNH may serve as a targeted antimicrobial therapy for CRC by inhibiting Fn and associated inflammation.
• These findings support the development of gut microbiota-targeted therapies for CRC.