TY - JOUR
T1 - Advancing the role of gamma-tocotrienol as proteasomes inhibitor
T2 - A quantitative proteomic analysis of MDA-MB-231 human breast cancer cells
AU - Ramdas, Premdass
AU - Radhakrishnan, Ammu Kutty
AU - Sani, Asmahani Azira Abdu
AU - Kumari, Mangala
AU - Rao, Jeya Seela Anandha
AU - Abdul-Rahman, Puteri Shafinaz
N1 - Funding Information:
Author Contributions: P.R., A.K.R., and P.S.A.-R. designed the project and acquired the funding, P.R., A.A.A.S., M.K., and J.S.A.R. performed bioinformatics analysis, P.R. and A.A.A.S. conducted the research investigation, A.R. and P.S.A.R. supervised the project. All authors significantly contributed to the writing and review of this research article. All authors have read and agreed to the published version of the manuscript.
Funding Information:
Funding: This work was supported with research grants from the Fundamental Research Grant Scheme (FRGS, FP016–2013B) from the Ministry of Higher Education, Malaysia, Frontier Research Grant UM (FRG, FG018–17AFR) and UM Research Grant (RG082/09AFR) from University Malaya, Malaysia.
Funding Information:
This work was supported with research grants from the Fundamental Research Grant Scheme (FRGS, FP016?2013B) from the Ministry of Higher Education, Malaysia, Frontier Research Grant UM (FRG, FG018?17AFR) and UM Research Grant (RG082/09AFR) from University Malaya, Malaysia.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Mass spectrometry
KW - Proteasomes
KW - Tocotrienols
KW - Vitamin E
UR - http://www.scopus.com/inward/record.url?scp=85077266323&partnerID=8YFLogxK
U2 - 10.3390/biom10010019
DO - 10.3390/biom10010019
M3 - Article
C2 - 31877708
AN - SCOPUS:85077266323
SN - 2218-273X
VL - 10
JO - Biomolecules
JF - Biomolecules
IS - 1
M1 - 19
ER -
