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

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Lipids

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 down-regulated 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.

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Abbreviations

APC:

antigen-presenting cell

FcRn:

IgG Fe receptor large subunit P51 precursor

IFITM-1:

interferon-inducible transmembrane protein-1

IFN-γ:

interferon-γ

MHC:

major histocompatibility

NK:

natural killer

TRF:

tocotrienol-rich fraction

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Authors and Affiliations

  1. Malaysian Palm Oil Board, Bandar Baru Bangi, 4300, Selangor, Malaysia

    Kalanithi Nesaretnam, Kanga Rani Selvaduray, Karin Reimann & Ghazali Razak

  2. National Institute for Food and Nutrition Research, Rome, Italy

    Roberto Ambra & Fabio Virgili

  3. International Medical University, Kuala Lumpur, Malaysia

    Ammu Radhakrishnan

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  1. Kalanithi Nesaretnam
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  2. Roberto Ambra
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  3. Kanga Rani Selvaduray
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  4. Ammu Radhakrishnan
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  6. Ghazali Razak
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  7. Fabio Virgili
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Correspondence to Kalanithi Nesaretnam.

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Nesaretnam, K., Ambra, R., Selvaduray, K.R. et al. Tocotrienol-rich fraction from palm oil affects gene expression in tumors resulting from MCF-7 cell inoculation in athymic mice. Lipids 39, 459–467 (2004). https://doi.org/10.1007/s11745-004-1251-1

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