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

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

  • Biomed Pharmacother. 2014 Oct;68(8):1105-15. doi: 10.1016/j.biopha.2014.10.006.
Su-Wen Lim 1,  Hwei-San Loh 2,  Kang Nee Ting 3,  Tracey D Bradshaw 4,  Nazariah A Zeenathul 5
Affiliations

Affiliations

  • 1 School of Biosciences, Faculty of Science, University of Nottingham Malaysia Campus, 43500 Semenyih, Malaysia. Electronic address: Lim.SuWen@nottingham.edu.my.
  • 2 School of Biosciences, Faculty of Science, University of Nottingham Malaysia Campus, 43500 Semenyih, Malaysia. Electronic address: Sandy.Loh@nottingham.edu.my.
  • 3 Department of Biomedical Sciences, Faculty of Science, University of Nottingham Malaysia Campus, 43500 Semenyih, Malaysia. Electronic address: Kang-Nee.Ting@nottingham.edu.my.
  • 4 School of Pharmacy, Faculty of Science, University of Nottingham, University Park, Nottingham NG7 2RD, UK. Electronic address: Tracey.Bradshaw@nottingham.ac.uk.
  • 5 Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 Serdang, Malaysia. Electronic address: zeenathul@upm.edu.my.
PMID: 25456851 DOI: 10.1016/j.biopha.2014.10.006
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.

Keywords

Antiproliferation; Apoptosis; Caspase-8; Cytochrome c; DNA damage; β-tocotrienol.

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