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

in BioImpacts : BI by Gang He, Mei Liu, Tang Cong Chen, Li Fen Huang, You Qiang Ke

TLDR

  • This study demonstrates that combining SBFI-26 with docetaxel enhances apoptosis in triple-negative breast cancer MDA-MB-231 cells by elevating intracellular ROS levels.

Abstract

Fatty acid binding protein 5 (FABP5) exhibits heightened expression levels in triple-negative breast cancer. The inhibitor of FABP5, Stony Brook fatty acid-binding protein inhibitor 26 (SBFI-26), has demonstrated the capacity to suppress cell proliferation, migration, and invasion. This study delves into the functional mechanism and impact of combining SBFI-26 with docetaxel in treating MDA-MB-231 cells of triple-negative breast cancer. Various concentrations of docetaxel and SBFI-26 were chosen for individual or combined treatments. The effects of SBFI-26, docetaxel, or their combination on cell cycle arrest and apoptosis were assessed using flow cytometry. Western blotting was utilised to detect the expression of apoptosis-related proteins, namely cysteinyl aspartate-specific proteases 3 (Caspase3), B cell leukemia/lymphoma 2 (Bcl-2), and Bcl-2 associated X (Bax), while intracellular reactive oxygen species (ROS) levels were determined using a fluorescence spectrophotometer. The IC50 values for SBFI-26 and docetaxel in inhibiting MDA-MB-231 cells were determined to be 106.1 μM and 86.14 nM, respectively. Significantly, the combination treatment augmented the proportion of G1 phase (apoptotic) cells by 3.67-fold compared to the control group (< 0.0001). Furthermore, the apoptosis rate in the combination group was 2.59-fold higher than that in the docetaxel group (< 0.0001) and demonstrated a significant increase of 1.82-fold compared with the SBFI-26 group (< 0.001). Analyses revealed a decrease in the protein expression of Bcl-2, while Bax and Caspase3 exhibited an increase in the combination group for MDA-MB-231 cells. Moreover, the combined treatment group demonstrated a 2.97-fold increase (< 0.0001) in ROS fluorescence intensity compared to the control group, a noteworthy 1.39-fold increase (< 0.01) compared to the SBFI-26 treatment group, and a substantial 1.70-fold increase (< 0.0001) compared to the docetaxel treatment group. These findings suggest that the co-administration of SBFI-26 with docetaxel effectively enhances apoptosis in triple-negative breast cancer MDA-MB-231 cells by elevating intracellular ROS levels.

Overview

  • The study investigates the combined effect of Stony Brook fatty acid-binding protein inhibitor 26 (SBFI-26) and docetaxel on MDA-MB-231 cells of triple-negative breast cancer, focusing on cell cycle arrest and apoptosis.
  • The main objective is to explore the functional mechanism of combining SBFI-26 with docetaxel in treating triple-negative breast cancer and its potential impact on cell proliferation, migration, and invasion.
  • The study employed various concentrations of docetaxel and SBFI-26 for individual or combined treatments, assessing the effects on cell cycle arrest, apoptosis, and apoptosis-related protein expression.

Comparative Analysis & Findings

  • The IC50 values for SBFI-26 and docetaxel were determined to be 106.1 μM and 86.14 nM, respectively.
  • The combination treatment significantly augmented the proportion of G1 phase (apoptotic) cells by 3.67-fold compared to the control group (< 0.0001).
  • The apoptosis rate in the combination group was 2.59-fold higher than that in the docetaxel group (< 0.0001) and demonstrated a significant increase of 1.82-fold compared with the SBFI-26 group (< 0.001).

Implications and Future Directions

  • The study suggests that the co-administration of SBFI-26 with docetaxel effectively enhances apoptosis in triple-negative breast cancer MDA-MB-231 cells by elevating intracellular ROS levels.
  • Future research could explore the potential therapeutic application of combining SBFI-26 with docetaxel in clinical trials and investigate the mechanisms underlying the anti-cancer effects of this combination.
  • The study highlights the need for further research to determine the optimal dosage and scheduling of SBFI-26 and docetaxel combination therapy for the treatment of triple-negative breast cancer.
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