Issue 11, 2014

Delta-tocotrienol induces apoptotic cell death via depletion of intracellular squalene in ED40515 cells

Abstract

Here, we examined the effect of tocotrienols (T3) on the growth of adult T-cell leukemia (ATL) cells. All three forms (β-, γ-, and δ-T3) inhibited cell proliferation in a dose-dependent manner; δ-T3 showed the strongest growth-inhibitory effect. δ-T3 increased the G1, G2/M, and subG1 populations and induced internucleosomal DNA fragmentation. δ-T3 treatment also increased the levels of cleaved caspase-3, -6, -7, -9, and poly-ADP ribose polymerase (PARP), and this was accompanied by downregulation of Bcl-2, Bcl-xL, and XIAP. Moreover, δ-T3 decreased nuclear p65 NF-κB levels, indicating downregulation of NF-κB activity. This cytotoxic effect of δ-T3 was abrogated by squalene (SQL) but not mevalonate (MVL), farnesyl diphosphate (FPP), geranylgeranyl diphosphate (GGPP), or cholesterol (CL). δ-T3 decreased intracellular SQL levels, and inhibition of de novo cholesterol synthesis did not affect the action of SQL. Furthermore, δ-T3 significantly decreased farnesyl-diphosphate farnesyltransferase 1 (FDFT1) expression. Taken together, it is evident that δ-T3, due to its ability to potently induce apoptosis via the depletion of intracellular SQL, shows the potential to be considered a therapeutic agent in patients with ATL.

Graphical abstract: Delta-tocotrienol induces apoptotic cell death via depletion of intracellular squalene in ED40515 cells

Article information

Article type
Paper
Submitted
18 Jul 2014
Accepted
25 Aug 2014
First published
26 Aug 2014

Food Funct., 2014,5, 2842-2849

Delta-tocotrienol induces apoptotic cell death via depletion of intracellular squalene in ED40515 cells

M. Yamasaki, M. Nishimura, Y. Sakakibara, M. Suiko, K. Morishita and K. Nishiyama, Food Funct., 2014, 5, 2842 DOI: 10.1039/C4FO00635F

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