Abstract

Tocotrienol, an analogue of vitamin E has been known for its numerous health benefits and anti-cancer effects. Of the four isoforms of tocotrienols, gamma-tocotrienol (γT3) has been frequently reported for their superior anti-tumorigenic activity in both in vitro and in vivo studies, when compared to its counterparts. In this study, the effect of γT3 treatment in the cytoplasmic and nuclear fraction of MDA-MB-231 human breast cancer cells were assessed using the label-free quantitative proteomics analysis. The cytoplasmic proteome results revealed the ability of γT3 to inhibit a group of proteasome proteins such as PSMA, PSMB, PSMD, and PSME. The inhibition of proteasome proteins is known to induce apoptosis in cancer cells. As such, the findings from this study suggest γT3 as a potential proteasome inhibitor that can overcome deficiencies in growth-inhibitory or pro-apoptotic molecules in breast cancer cells. The nuclear proteome results revealed the involvement of important nuclear protein complexes which hardwire the anti-tumorigenesis mechanism in breast cancer following γT3 treatment. In conclusion, this study uncovered the advancing roles of γT3 as potential proteasomes inhibitor that can be used for the treatment of breast cancer.

Highlights

  • Breast cancer (BC) is the most common malignancy in women around the world

  • MDA-MB-231 to the γT3 treatment, the analysis that most of theseofproteins are grouped under acetylation, nuclear proteins in ribonucleic, response to the treatment, the analysis showed that proteins are nucleotide binding, andγT3 transport proteins, which confirmed the most natureofofthese nuclear fraction grouped under acetylation, nucleotide binding, ribonucleic, and proteins, which confirmed used in this study (Figure 3)

  • Our data indicates that gamma-tocotrienol is a novel proteasome inhibitor adding to its anti-cancer properties

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Summary

Introduction

Breast cancer (BC) is the most common malignancy in women around the world. According to GLOBOCAN 2018, breast cancer is the most common cancer in women; accounting for 11.6% of all cancers [1]. In 2018, about 2.1 million newly diagnosed female breast cancer cases were reported worldwide, which accounts for about 1 in 4 breast cancer cases among women [1]. The same authors reported that there were 626,679 (6.6%) cases of deaths due to breast cancer worldwide [1]. The incidence of breast cancer in women worldwide was reported to be 24.2%, while the mortality rate. Biomolecules 2020, 10, 19 was estimated to be 15% [1]. A similar trend was observed in the United States of America (USA)

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