Tocotrienol‐rich fraction from palm oil affects gene expression in tumors resulting from MCF‐7 cell inoculation in athymic mice

Abstract

It has recently been shown that tocotrienols are the components of vitamin E responsible for inhibiting the growth of human breast cancer cells in vitro, through an estrogen-independent mechanism. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. To investigate the molecular basis of the effect of tocotrienols, we injected MCF-7 breast cancer cells into athymic nude mice. Mice were fed orally with 1 mg/d of tocotrienol-rich fraction (TRF) for 20 wk. At end of the 20 wk, there was a significant delay in the onset, incidence, and size of the tumors in nude mice supplemented with TRF compared with the controls. At autopsy, the tumor tissue was excised and analyzed for gene expression by means of a cDNA array technique. Thirty out of 1176 genes were significantly affected. Ten genes were downregulated and 20 genes up-regulated with respect to untreated animals, and some genes in particular were involved in regulating the immune system and its function. The expression of the interferon-inducible transmembrane protein-1 gene was significantly up-regulated in tumors excised from TRF-treated animals compared with control mice. Within the group of genes related to the immune system, we also found that the CD59 glycoprotein precursor gene was up-regulated. Among the functional class of intracellular transducers/effectors/modulators, the c-myc gene was significantly down-regulated in tumors by TRF treatment. Our observations indicate that TRF supplementation significantly and specifically affects MCF-7 cell response after tumor formation in vivo and therefore the host immune function. The observed effect on gene expression is possibly exerted independently from the antioxidant activity typical of this family of molecules.

Why tocotrienols work better: insights into the in vitro anti-cancer mechanism of vitamin E

“…This is true for either cytoprotection or anti-cancer activity of T3 which show concentration-dependent functional regulation of different signaling routes and groups of genes (Nesaretnam et al 2004;Aisa et al 2006;Yap et al 2008) (Fig. 1).…”

“…In vivo studies so far performed in immunocompromised animals after ectopic implantation of breast cancer cells (Nesaretnam et al 2004) as well as other studies that investigated tumor mass growth and vascularization in other models of ectopic implants (Nakagawa et al 2007;Shibata et al 2009;Weng-Yew et al 2009), have not provided an affordable model system to clarify this point. These studies were based on the supplementation of high dosages (between 1 and 10 mg/day) of T3 under the form of palm oil derived T3-rich fraction (TRF) that provided different contributions to the observed anti-cancer effects by the individual forms of T3 contained in this type formulation.…”

Gamma‐tocotrienol as an effective agent in targeting prostate cancer stem cell‐like population

“…Increasing evidence suggests that T3s possess substantial anticancer effects in many types of cancers, including breast, liver, lung, gastric, colon, skin and prostate cancer. [11][12][13][14][15][16][17] Recently, we have reported that among the four isoforms (a, b, c and d) of T3, the gamma isoform (c-T3) possesses the most potent anticancer effect against prostate cancer cells. 18 By comparing the effect of the four T3 isomers on nonmalignant prostate epithelial cells and prostate cancer cell lines, we found that c-T3 is more effective in inhibiting both the growth and survival of prostate cancer cells.…”

γ-Tocotrienol suppresses prostate cancer cell proliferation and invasion through multiple-signalling pathways

“…Apart from tocotrienol's antioxidant, anti-inflammatory, antiangiogenic, antineurodegeneration, antihypercholesterolemic and antimicrobial properties, emerging in vitro and in vivo evidences have manifested the anticancer activity of tocotrienol on numerous human cancer cells including prostate, breast, colon, liver and gastric (Agarwal et al, 2004;Nesaretnam et al, 2004;Sylvester and Shah, 2005;Eitsuka et al, 2006;Kumar et al, 2006;McAnally et al, 2007) (reviewed in (Sen et al, 2007)). For example, a recent study (Srivastava and Gupta, 2006) has demonstrated that treatment of PCa cell lines (LNCaP, DU145, PC-3) with tocotrienol-rich fraction (TRF) resulted in significant decreases in cell viability and colony formation capability.…”