title: Antiproliferation and induction of caspase-8-dependent mitochondria-mediated apoptosis by β-tocotrienol in human lung and brain cancer cell lines.
abstract: 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.
authors.affiliation: School of Biosciences, Faculty of Science, University of Nottingham Malaysia Campus, 43500 Semenyih, Malaysia. Electronic address: Lim.SuWen@nottingham.edu.my.
authors.forename: Su-Wen
authors.initials: SW
authors.lastname: Lim
authors.affiliation: School of Biosciences, Faculty of Science, University of Nottingham Malaysia Campus, 43500 Semenyih, Malaysia. Electronic address: Sandy.Loh@nottingham.edu.my.
authors.forename: Hwei-San
authors.initials: HS
authors.lastname: Loh
authors.affiliation: Department of Biomedical Sciences, Faculty of Science, University of Nottingham Malaysia Campus, 43500 Semenyih, Malaysia. Electronic address: Kang-Nee.Ting@nottingham.edu.my.
authors.forename: Kang Nee
authors.initials: KN
authors.lastname: Ting
authors.affiliation: School of Pharmacy, Faculty of Science, University of Nottingham, University Park, Nottingham NG7 2RD, UK. Electronic address: Tracey.Bradshaw@nottingham.ac.uk.
authors.forename: Tracey D
authors.initials: TD
authors.lastname: Bradshaw
authors.affiliation: Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 Serdang, Malaysia. Electronic address: zeenathul@upm.edu.my.
authors.forename: Nazariah A
authors.initials: NA
authors.lastname: Zeenathul
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D053181:Caspase 8 / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D014810:Vitamin E; C082089:tocotrienol, beta; D053181:Caspase 8
keywords: Antiproliferation; Apoptosis; Caspase-8; Cytochrome c; DNA damage; β-tocotrienol