Aronia Berry Extract Inhibits Cancer Stemness and Overcomes 5-Fluorouracil Resistance by Targeting TLR3/NF-κB...

Area of Science:

• Oncology
• Pharmacology
• Natural Products Chemistry

Background:

• Colorectal cancer (CRC) presents significant challenges due to limited chemotherapy efficacy, particularly acquired resistance to 5-fluorouracil (5-FU).
• Aronia berry extract (ABE), rich in phenolic compounds, exhibits potential anticancer and chemosensitizing properties.
• Understanding ABE's role in overcoming 5-FU resistance in CRC is crucial for developing novel therapeutic strategies.

Purpose of the Study:

• To investigate ABE's efficacy in overcoming 5-FU resistance in CRC.
• To elucidate the molecular mechanisms by which ABE exerts its therapeutic effects.
• To evaluate ABE as a potential adjunctive therapy for 5-FU-resistant CRC.

Main Methods:

• In vitro studies using 5-FU-resistant CRC cell lines to assess synergistic effects of ABE and 5-FU.
• Genome-wide transcriptomic profiling to identify chemoresistance pathways and ABE targets.
• Validation using patient-derived 3D organoids (PDOs) and functional inhibition of Toll-like receptor 3 (TLR3).

Main Results:

• ABE and 5-FU combination therapy significantly reduced 5-FU effective concentration and suppressed CRC cell viability, migration, and invasion.
• ABE decreased cancer stemness markers (CD44, Nanog, Oct4) and inhibited spheroid growth via TLR3.
• PDO experiments confirmed reduced organoid growth, survival, and NF-κB expression with ABE treatment.

Conclusions:

• ABE effectively overcomes 5-FU resistance in CRC by targeting the TLR3/NF-κB signaling axis.
• ABE demonstrates potential as a safe and accessible adjunctive strategy to enhance CRC chemotherapy.
• This research provides a mechanistic basis for using ABE in treating 5-FU-resistant colorectal cancer.