Abstract
Experimental studies were conducted to compare the relative effects of γ-tocotrienol, a natural isoform within the vitamin E family of compounds, with established galectin-3 inhibitor β-lactose, on galectin-3 levels and distribution in highly metastatic human MDA-MB-231, and mouse + SA and TS/A breast cancer cell lines. In contrast to β-lactose, γ-tocotrienol displays a dual-mode binding profile with the carbohydrate recognition domain and hydrophobic pocket located on galectin-3, as determined using Schrödinger molecular modeling. However, treatment with either γ-tocotrienol or β-lactose induces a significant decrease in galectin-3 expression, oligomerization, and a corresponding decrease in fibronectin fibril and lamellipodial protrusion formation, an indication of treatment-induced reversal in epithelial-mesenchymal transition (EMT). These same treatments also caused a significant decrease in galectin-3 Fluorescence Resonance Energy Transfer (FRET) signaling, as compared to the control group, demonstrating the intricate role of galectin-3 in modulating EMT in metastatic breast cancer cells. Combined treatment of doxorubicin with either γ-tocotrienol or β-lactose results in a large increase in doxorubicin levels in the nuclei of metastatic breast cancer cells, the primary site of action for this chemotherapeutic agent. Taken together these findings demonstrate that γ-tocotrienol-induced reversal of EMT in metastatic breast cancer cells is mediated, at least in part, by a disruption in the galectin-3 expression, distribution and function.
Data availability
All data generated or analyzed during this study was conducted at the University of Louisiana Monroe. This includes data from Schrödinger molecular docking outputs, stain-free western blot source files generated in Image Lab software, confocal microscopy images generated in ZEN Zeiss Microscopy software, and FRET microplate reader datasets generated in I-control 2.0 software. The final data analysis is included in this article. Additional raw data or intermediate analysis files are available from the corresponding author upon request.
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Acknowledgements
The authors would also like to thank Dr. Karen P. Briski for her generous assistance and use of the laser confocal microscope.
Funding
This research was supported in part by a grant from the Louisiana Cancer Foundation and the Mark and Mildred Maurer Cancer Research Enhancement Endowed Fund.
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Jessie J. Grazier designed and conducted all experiments, including data acquisition and analysis, and drafted the manuscript. Paul W. Sylvester obtained the necessary materials and reagents for the study and contributed to manuscript editing and revision. Both authors approved the final version of the manuscript.
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Grazier, J.J., Sylvester, P.W. γ-Tocotrienol inhibition of galectin-3 expression, distribution and oligomerization in highly metastatic breast cancer cells. Sci Rep (2026). https://doi.org/10.1038/s41598-026-45608-9
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DOI: https://doi.org/10.1038/s41598-026-45608-9
