Antiproliferation and induction of caspase-8-dependent mitochondria-mediated apoptosis by β-tocotrienol in human lung and brain cancer cell lines

The pure vitamin isomer, β-tocotrienol has the least abundance among the other vitamin E isomers that are present in numerous plants. Hence, it is very scarcely studied for its bioactivity. In this study, the antiproliferative effects and primary apoptotic mechanisms of β-tocotrienol on human lung a...

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Main Authors: Lim, Su Wen, Loh, Hwei San, Ting, Kang Nee, Bradshaw, Tracey Dawn, Allaudin, Zeenathul Nazariah
Format: Article
Language:English
Published: Elsevier 2014
Online Access:http://psasir.upm.edu.my/id/eprint/36497/
http://psasir.upm.edu.my/id/eprint/36497/1/Exotic%20berries%20as%20a%20functional%20food.pdf
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author Lim, Su Wen
Loh, Hwei San
Ting, Kang Nee
Bradshaw, Tracey Dawn
Allaudin, Zeenathul Nazariah
author_facet Lim, Su Wen
Loh, Hwei San
Ting, Kang Nee
Bradshaw, Tracey Dawn
Allaudin, Zeenathul Nazariah
author_sort Lim, Su Wen
building UPM Institutional Repository
collection Online Access
description The pure vitamin isomer, β-tocotrienol has the least abundance among the other vitamin E isomers that are present in numerous plants. Hence, it is very scarcely studied for its bioactivity. In this study, the antiproliferative effects and primary apoptotic mechanisms of β-tocotrienol on human lung adenocarcinoma A549 and glioblastoma U87MG cells were investigated. It was evidenced that β-tocotrienol had inhibited the growth of both A549 (GI50=1.38±0.334μM) and U87MG (GI50=2.53±0.604μM) cells at rather low concentrations. Cancer cells incubated with β-tocotrienol were also found to exhibit hallmarks of apoptotic morphologies including membrane blebbing, chromatin condensation and formation of apoptotic bodies. The apoptotic properties of β-tocotrienol in both A549 and U87MG cells were the results of its capability to induce significant (P<0.05) double-strand DNA breaks (DSBs) without involving single-strand DNA breaks (SSBs). β-Tocotrienol is said to induce activation of caspase-8 in both A549 and U87MG cells guided by no activation when caspase-8 inhibitor, z-IETD-fmk was added. Besides, disruption on the mitochondrial membrane permeability of the cells in a concentration- and time-dependent manner had occurred. The induction of apoptosis by β-tocotrienol in A549 and U87MG cells was confirmed to involve both the death-receptor mediated and mitochondria-dependent apoptotic pathways. These findings could potentiate the palm oil derived β-tocotrienol to serve as a new anticancer agent for treating human lung and brain cancers.
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spelling upm-364972019-10-30T07:21:39Z http://psasir.upm.edu.my/id/eprint/36497/ Antiproliferation and induction of caspase-8-dependent mitochondria-mediated apoptosis by β-tocotrienol in human lung and brain cancer cell lines Lim, Su Wen Loh, Hwei San Ting, Kang Nee Bradshaw, Tracey Dawn Allaudin, Zeenathul Nazariah The pure vitamin isomer, β-tocotrienol has the least abundance among the other vitamin E isomers that are present in numerous plants. Hence, it is very scarcely studied for its bioactivity. In this study, the antiproliferative effects and primary apoptotic mechanisms of β-tocotrienol on human lung adenocarcinoma A549 and glioblastoma U87MG cells were investigated. It was evidenced that β-tocotrienol had inhibited the growth of both A549 (GI50=1.38±0.334μM) and U87MG (GI50=2.53±0.604μM) cells at rather low concentrations. Cancer cells incubated with β-tocotrienol were also found to exhibit hallmarks of apoptotic morphologies including membrane blebbing, chromatin condensation and formation of apoptotic bodies. The apoptotic properties of β-tocotrienol in both A549 and U87MG cells were the results of its capability to induce significant (P<0.05) double-strand DNA breaks (DSBs) without involving single-strand DNA breaks (SSBs). β-Tocotrienol is said to induce activation of caspase-8 in both A549 and U87MG cells guided by no activation when caspase-8 inhibitor, z-IETD-fmk was added. Besides, disruption on the mitochondrial membrane permeability of the cells in a concentration- and time-dependent manner had occurred. The induction of apoptosis by β-tocotrienol in A549 and U87MG cells was confirmed to involve both the death-receptor mediated and mitochondria-dependent apoptotic pathways. These findings could potentiate the palm oil derived β-tocotrienol to serve as a new anticancer agent for treating human lung and brain cancers. Elsevier 2014-10 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/36497/1/Exotic%20berries%20as%20a%20functional%20food.pdf Lim, Su Wen and Loh, Hwei San and Ting, Kang Nee and Bradshaw, Tracey Dawn and Allaudin, Zeenathul Nazariah (2014) Antiproliferation and induction of caspase-8-dependent mitochondria-mediated apoptosis by β-tocotrienol in human lung and brain cancer cell lines. Biomedicine & Pharmacotherapy, 68 (8). pp. 1105-1115. ISSN 0753-3322; ESSN: 1950-6007 10.1016/j.biopha.2014.10.006
spellingShingle Lim, Su Wen
Loh, Hwei San
Ting, Kang Nee
Bradshaw, Tracey Dawn
Allaudin, Zeenathul Nazariah
Antiproliferation and induction of caspase-8-dependent mitochondria-mediated apoptosis by β-tocotrienol in human lung and brain cancer cell lines
title Antiproliferation and induction of caspase-8-dependent mitochondria-mediated apoptosis by β-tocotrienol in human lung and brain cancer cell lines
title_full Antiproliferation and induction of caspase-8-dependent mitochondria-mediated apoptosis by β-tocotrienol in human lung and brain cancer cell lines
title_fullStr Antiproliferation and induction of caspase-8-dependent mitochondria-mediated apoptosis by β-tocotrienol in human lung and brain cancer cell lines
title_full_unstemmed Antiproliferation and induction of caspase-8-dependent mitochondria-mediated apoptosis by β-tocotrienol in human lung and brain cancer cell lines
title_short Antiproliferation and induction of caspase-8-dependent mitochondria-mediated apoptosis by β-tocotrienol in human lung and brain cancer cell lines
title_sort antiproliferation and induction of caspase-8-dependent mitochondria-mediated apoptosis by β-tocotrienol in human lung and brain cancer cell lines
url http://psasir.upm.edu.my/id/eprint/36497/
http://psasir.upm.edu.my/id/eprint/36497/
http://psasir.upm.edu.my/id/eprint/36497/1/Exotic%20berries%20as%20a%20functional%20food.pdf