Tocotrienols Modulate Breast Cancer Secretomes and Affect Cancer-Signaling Pathways in MDA-MB-231 Cells: A Label-Free Quantitative Proteomic Analysis

Ramdas, Premdass and Radhakrishnan, Ammu Kutty and Abdu Sani, Asmahani Azira and Abdul-Rahman, Puteri Shafinaz (2019) Tocotrienols Modulate Breast Cancer Secretomes and Affect Cancer-Signaling Pathways in MDA-MB-231 Cells: A Label-Free Quantitative Proteomic Analysis. Nutrition and Cancer, 71 (8). pp. 1263-1271. ISSN 0163-5581, DOI https://doi.org/10.1080/01635581.2019.1607407.

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Official URL: https://doi.org/10.1080/01635581.2019.1607407

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. © 2019, © 2019 Taylor & Francis Group, LLC.

Item Type: Article
Funders: Fundamental Research Grant Scheme (FRGS, FP016?2013B) from the Ministry of Higher Education, Malaysia, Postgraduate Research Grant (PPP, PG201–2015B), Frontier Research Grant UM (FRG, FG018–17AFR) from University Malaya, Malaysia
Uncontrolled Keywords: Tocotrienols; Vitamin E; Fraction TRF
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 06 Feb 2020 01:18
Last Modified: 06 Feb 2020 01:18
URI: http://eprints.um.edu.my/id/eprint/23684

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