IMR Press / FBL / Volume 10 / Issue 1 / DOI: 10.2741/1565

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Mechanisms mediating the antiproliferative and apoptotic effects of vitamin E in mammary cancer cells
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1 School of Pharmacy, 700 University Avenue, University of Louisiana at Monroe, Monroe, LA 71209-0470, USA

Academic Editor: Sushanta K. Banerjee

Front. Biosci. (Landmark Ed) 2005, 10(1), 699–709; https://doi.org/10.2741/1565
Published: 1 January 2005
(This article belongs to the Special Issue Growth factors and cancer)
Abstract

Tocopherols and tocotrienol represent the two subgroups within the vitamin E family of compounds, but only tocotrienols display potent anticancer activity at doses that have little or no effect on normal cell growth or function. Tocotrienols are potent antioxidants, but antitumor activity is independent of antioxidant activity. The exact reason why tocotrienols are more potent than tocopherols is not completely understood, but at least part of the reason is because of greater cellular accumulation. Furthermore, dose-response studies show that growth inhibitory doses of tocotrienols are 5-6 times lower than their corresponding lethal doses, suggesting that the antiproliferative and cytotoxic effects of tocotrienols are mediated through different mechanisms. Recent studies showed that tocotrienol-induced programmed cell death (apoptosis) results from the activation of specific intracellular cysteine proteases (caspases) associated with death receptor activation and signal transduction. Furthermore, combined treatment with specific caspase inhibitors blocked the cytotoxic effects of tocotrienols in malignant mammary epithelial cells. In contrast, tocotrienol inhibition of cell proliferation appears to involve the suppression of multiple hormone- and growth factor-receptor mitogenic signaling pathways. Although additional studies are required to clarify the intracellular mechanisms mediating the anticancer effects of tocotrienols, experimental evidence strongly suggests that dietary supplementation of tocotrienols may provide significant health benefits in lowering the risk of breast cancer in women.

Keywords
vitamin E
Tocotrienols
Mammary Cancer
Apoptosis
Death Receptors
Mitochondrial Stress
Caspase
PI3K
Akt
and NfkappaB
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