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Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells

Background: Tocotrienols, especially the gamma isomer was discovered to possess cytotoxic effects associated with the induction of apoptosis in numerous cancers. Individual tocotrienol isomers are believed to induce dissimilar apoptotic mechanisms in different cancer types. This study was aimed to c...

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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: BioMed Central 2014
Online Access:http://psasir.upm.edu.my/id/eprint/36957/1/36957.pdf
http://psasir.upm.edu.my/id/eprint/36957/
http://www.biomedcentral.com/1472-6882/14/469/abstract
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spelling my.upm.eprints.369572019-10-30T07:16:10Z http://psasir.upm.edu.my/id/eprint/36957/ Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells Lim, Su Wen Loh, Hwei San Ting, Kang Nee Bradshaw, Tracey Dawn Allaudin, Zeenathul Nazariah Background: Tocotrienols, especially the gamma isomer was discovered to possess cytotoxic effects associated with the induction of apoptosis in numerous cancers. Individual tocotrienol isomers are believed to induce dissimilar apoptotic mechanisms in different cancer types. This study was aimed to compare the cytotoxic potency of alpha-, gamma- and delta-tocotrienols, and to explore their resultant apoptotic mechanisms in human lung adenocarcinoma A549 and glioblastoma U87MG cells which are scarcely researched. Methods: The cytotoxic effects of alpha-, gamma- and delta-tocotrienols in both A549 and U87MG cancer cells were first determined at the cell viability and morphological aspects. DNA damage types were then identified by comet assay and flow cytometric study was carried out to support the incidence of apoptosis. The involvements of caspase-8, Bid, Bax and mitochondrial membrane permeability (MMP) in the execution of apoptosis were further expounded. Results: All tocotrienols inhibited the growth of A549 and U87MG cancer cells in a concentration- and time-dependent manner. These treated cancer cells demonstrated some hallmarks of apoptotic morphologies, apoptosis was further confirmed by cell accumulation at the pre-G1 stage. All tocotrienols induced only double strand DNA breaks (DSBs) and no single strand DNA breaks (SSBs) in both treated cancer cells. Activation of caspase-8 leading to increased levels of Bid and Bax as well as cytochrome c release attributed by the disruption of mitochondrial membrane permeability in both A549 and U87MG cells were evident. Conclusions: This study has shown that delta-tocotrienol, in all experimental approaches, possessed a higher efficacy (shorter induction period) and effectiveness (higher induction rate) in the execution of apoptosis in both A549 and U87MG cancer cells as compared to alpha- and gamma-tocotrienols. Tocotrienols in particular the delta isomer can be an alternative chemotherapeutic agent for treating lung and brain cancers. BioMed Central 2014 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/36957/1/36957.pdf Lim, Su Wen and Loh, Hwei San and Ting, Kang Nee and Bradshaw, Tracey Dawn and Allaudin, Zeenathul Nazariah (2014) Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells. BMC Complementary and Alternative Medicine, 14. art. no. 469. pp. 1-18. ISSN 1472-6882 http://www.biomedcentral.com/1472-6882/14/469/abstract 10.1186/1472-6882-14-469
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description Background: Tocotrienols, especially the gamma isomer was discovered to possess cytotoxic effects associated with the induction of apoptosis in numerous cancers. Individual tocotrienol isomers are believed to induce dissimilar apoptotic mechanisms in different cancer types. This study was aimed to compare the cytotoxic potency of alpha-, gamma- and delta-tocotrienols, and to explore their resultant apoptotic mechanisms in human lung adenocarcinoma A549 and glioblastoma U87MG cells which are scarcely researched. Methods: The cytotoxic effects of alpha-, gamma- and delta-tocotrienols in both A549 and U87MG cancer cells were first determined at the cell viability and morphological aspects. DNA damage types were then identified by comet assay and flow cytometric study was carried out to support the incidence of apoptosis. The involvements of caspase-8, Bid, Bax and mitochondrial membrane permeability (MMP) in the execution of apoptosis were further expounded. Results: All tocotrienols inhibited the growth of A549 and U87MG cancer cells in a concentration- and time-dependent manner. These treated cancer cells demonstrated some hallmarks of apoptotic morphologies, apoptosis was further confirmed by cell accumulation at the pre-G1 stage. All tocotrienols induced only double strand DNA breaks (DSBs) and no single strand DNA breaks (SSBs) in both treated cancer cells. Activation of caspase-8 leading to increased levels of Bid and Bax as well as cytochrome c release attributed by the disruption of mitochondrial membrane permeability in both A549 and U87MG cells were evident. Conclusions: This study has shown that delta-tocotrienol, in all experimental approaches, possessed a higher efficacy (shorter induction period) and effectiveness (higher induction rate) in the execution of apoptosis in both A549 and U87MG cancer cells as compared to alpha- and gamma-tocotrienols. Tocotrienols in particular the delta isomer can be an alternative chemotherapeutic agent for treating lung and brain cancers.
format Article
author Lim, Su Wen
Loh, Hwei San
Ting, Kang Nee
Bradshaw, Tracey Dawn
Allaudin, Zeenathul Nazariah
spellingShingle Lim, Su Wen
Loh, Hwei San
Ting, Kang Nee
Bradshaw, Tracey Dawn
Allaudin, Zeenathul Nazariah
Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells
author_facet Lim, Su Wen
Loh, Hwei San
Ting, Kang Nee
Bradshaw, Tracey Dawn
Allaudin, Zeenathul Nazariah
author_sort Lim, Su Wen
title Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells
title_short Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells
title_full Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells
title_fullStr Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells
title_full_unstemmed Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells
title_sort cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells
publisher BioMed Central
publishDate 2014
url http://psasir.upm.edu.my/id/eprint/36957/1/36957.pdf
http://psasir.upm.edu.my/id/eprint/36957/
http://www.biomedcentral.com/1472-6882/14/469/abstract
_version_ 1651869049420775424
score 13.211869

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