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Tocotrienols Modulate Breast Cancer Secretomes and Affect Cancer-Signaling Pathways in MDA-MB-231 Cells: A Label-Free
Premdass Ramdas1,2, Ammu Kutty Radhakrishnan3, Asmahani Azira Abdu Sani4
1Department of Molecular Medicine, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
Abstract:
Tocotrienols (T3), a family of vitamin E, are reported to possess potent anti-cancer effects but the molecular mechanisms behind these effects still remain unclear. The aim of this study was to investigate how T3 exert anti-cancer effects on MDA-MB-231 human breast cancer cells. The MDA-MB-231 cells were chosen for this study as they are triple-negative and highly metastatic cells, which form aggressive tumors in experimental models. The MDA-MB-231 cells were treated with varying concentrations (0-20 µg mL-1) of gamma (γ) or delta (δ) T3 and the secretome profiles of these cells treated with half maximal inhibitory concentration (IC50) of γT3 (5.8 µg mL-1) or δT3 (4.0 µg mL-1) were determined using label-free quantitative proteomic strategy. A total of 103, 174 and 141 proteins were identified with ProteinLynx Global Server (PLGS) score of more than 200 and above 25% sequence coverage in the untreated control and T3-treated cell culture supernatant respectively. A total of 18 proteins were dysregulated between untreated control and T3 (δT3 or γT3) treated conditions. The results showed that T3 treatment downregulated the exogenous Cathepsin D and Serpine1 proteins but upregulated Profilin-1 protein, which play a key role in breast cancer in the MDA-MB-231 cells. These findings strongly suggest that T3 may induce differential expression of secreted proteins involved in the cytoskeletal regulation of RHO GTPase signaling pathway.
Insights
Tocotrienols (T3), a form of vitamin E, show anti-cancer effects by altering protein expression in aggressive breast cancer cells. This study reveals T3
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Tocotrienols (T3), a family of vitamin E, are known for potent anti-cancer properties.
- The precise molecular mechanisms underlying T3's anti-cancer effects, particularly in aggressive cancer types, require further elucidation.
Purpose of the Study:
- To investigate the anti-cancer effects of gamma (γ) and delta (δ) Tocotrienols (T3) on MDA-MB-231 human breast cancer cells.
- To determine the impact of T3 treatment on the secretome profiles of these aggressive, triple-negative breast cancer cells.
Main Methods:
- MDA-MB-231 cells were treated with varying concentrations of γT3 and δT3.
- Label-free quantitative proteomic analysis was employed to identify and quantify proteins in the cell culture supernatant.
- Secretome profiles were analyzed at the half maximal inhibitory concentration (IC50) for both γT3 and δT3.
Main Results:
- Proteomic analysis identified a significant number of proteins in the cell supernatant.
- T3 treatment resulted in the differential expression of 18 proteins.
- Specifically, T3 downregulated Cathepsin D and Serpine1 while upregulating Profilin-1 in MDA-MB-231 cells.
Conclusions:
- Tocotrienols (T3) modulate the expression of key secreted proteins involved in breast cancer progression.
- The findings suggest T3 influences cytoskeletal regulation via the RHO GTPase signaling pathway.
- T3 demonstrates potential as a therapeutic agent against aggressive breast cancers like triple-negative MDA-MB-231 cells.
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