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, beta-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 beta-tocotrienol on human lung adenocarcinoma A549 and glioblastoma U87MG cells were investigated. It was evidenced that beta-tocotrienol had inhibited the growth of both A549 (GI(50) = 1.38 +/- 0.334 mM) and U87MG (GI(50) = 2.53 +/- 0.604 mM) cells at rather low concentrations. Cancer cells incubated with b-tocotrienol were also found to exhibit hallmarks of apoptotic morphologies including membrane blebbing, chromatin condensation and formation of apoptotic bodies. The apoptotic properties of beta-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). beta-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 beta-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 beta-tocotrienol to serve as a new anticancer agent for treating human lung and brain cancers. (C) 2014 Elsevier Masson SAS. All rights reserved.