SBFI-26 enhances apoptosis in docetaxel-treated triple-negative breast cancer cells by increasing ROS levels

Introduction:
Fatty acid binding protein 5 (FABP5) is overexpressed in triple-negative breast cancer (TNBC). Its inhibitor, Stony Brook fatty acid-binding protein inhibitor 26 (SBFI-26), has been shown to suppress cell proliferation, migration, and invasion. This study investigates the mechanism and therapeutic potential of combining SBFI-26 with docetaxel in treating MDA-MB-231 TNBC cells.
Methods:
MDA-MB-231 cells were treated with varying concentrations of docetaxel and SBFI-26, either alone or in combination. Flow cytometry was used to evaluate cell cycle distribution and apoptosis. Western blotting assessed the expression of apoptosis-related proteins, including Caspase-3, Bcl-2, and Bax. Intracellular reactive oxygen species (ROS) levels were measured using a fluorescence spectrophotometer.
Results:
The IC₅₀ values for SBFI-26 and docetaxel were 106.1 μM and 86.14 nM, respectively. Combined treatment significantly increased the proportion of G1 phase cells by 3.67-fold compared to control (P < 0.0001). Apoptosis rates were 2.59-fold higher than with docetaxel alone (P < 0.0001) and 1.82-fold higher than with SBFI-26 alone (P < 0.001). The combination also reduced Bcl-2 expression while upregulating Bax and Caspase-3. ROS levels in the combination group increased 2.97-fold versus control (P < 0.0001), 1.39-fold compared to SBFI-26 (P < 0.01), and 1.70-fold compared to docetaxel (P < 0.0001).
Conclusion:
Co-treatment with SBFI-26 and docetaxel enhances apoptosis in TNBC MDA-MB-231 cells, likely through elevated intracellular ROS and modulation of apoptotic signaling pathways.