Bakuchiol Enhances 5-Fluorouracil Efficacy in Colorectal Cancer Cells via a ROS-Dependent Mechanism Involving...

Area of Science:

• Oncology
• Pharmacology
• Cell Biology

Background:

• 5-fluorouracil (5-FU) resistance is a significant challenge in colorectal cancer (CRC) treatment.
• Combination therapies are crucial for enhancing 5-FU efficacy.
• Bakuchiol (BAK), a natural compound, possesses antioxidant and pro-oxidant properties that may influence cancer cell response.

Purpose of the Study:

• To investigate the combined effects of 5-FU and BAK on colorectal cancer cells.
• To elucidate the mechanisms underlying the enhanced cytotoxicity of the 5-FU and BAK combination.
• To assess the role of redox balance and apoptosis in the observed effects.

Main Methods:

• Cytotoxicity assays (IC50 determination) were performed on DLD-1 and HT-29 CRC cell lines.
• Flow cytometry was used to analyze apoptosis via extrinsic and intrinsic pathways (caspase activity, mitochondrial membrane potential).
• Intracellular reactive oxygen species (ROS) levels were measured, and the effect of antioxidant pre-treatment was evaluated.

Main Results:

• Co-treatment with 5-FU and BAK significantly reduced the IC50 of 5-FU, demonstrating enhanced anticancer effects.
• The combination treatment induced apoptosis through both extrinsic and intrinsic pathways, involving caspase activation and mitochondrial dysfunction.
• Increased ROS levels were observed, indicating redox imbalance, and antioxidant pre-treatment attenuated these effects, confirming a causal role for oxidative stress.

Conclusions:

• Bakuchiol enhances 5-FU efficacy in colorectal cancer cells by inducing ROS-dependent apoptosis via mitochondrial and caspase pathways.
• The combination therapy shows greater effectiveness than monotherapy, particularly in DLD-1 cells.
• Cell-line-specific differences in redox adaptation, including autophagy induction, were noted.