Tocotrienols and breast cancer: the evidence to date

Abstract

Breast cancer is the second most frequent cancer affecting women worldwide after lung cancer. The toxicity factor associated with synthetic drugs has turned the attention toward natural compounds as the primary focus of interest as anticancer agents. Vitamin E derivatives consisting of the well-established tocopherols and their analogs namely tocotrienols have been extensively studied due to their remarkable biological properties. While tocopherols have failed to offer protection, tocotrienols, in particular, a-, d-, and c-tocotrienols alone and in combination have demonstrated anticancer properties. The discovery of the antiangiogenic, antiproliferative, and apoptotic effects of tocotrienols, as well as their role as an inducer of immunological functions, not only reveals a new horizon as a potent antitumor agent but also reinforces the notion that tocotrienols are indeed more than antioxidants. On the basis of a transcriptomic platform, we have recently demonstrated a novel mechanism for tocotrienol activity that involves estrogen receptor (ER) signaling. In silico simulations and in vitro binding analyses indicate a high affinity of specific forms of tocotrienols for ERb, but not for ERa. Moreover, we have demonstrated that specific tocotrienols increase ERb translocation into the nucleus which, in turn, activates the expression of estrogenresponsive genes (MIC-1, EGR-1 and Cathepsin D) in breast cancer cells only expressing ERb cells (MDA-MB-231) and in cells expressing both ER isoforms (MCF-7). The binding of specific tocotrienol forms to ERb is associated with the alteration of cell morphology, caspase-3 activation, DNA fragmentation, and apoptosis. Furthermore, a recently concluded clinical trial seems to suggest that tocotrienols in combination with tamoxifen may have the potential to extend breast cancer-specific survival.

Autophagy inhibitor 3-methyladenine potentiates apoptosis induced by dietary tocotrienols in breast cancer cells

“…T3s have been shown to inhibit the growth of various cancer cells including breast cancer without affecting the growth of normal cells [5–8]. T3s have been evaluated in vitro and in vivo as powerful cancer chemotherapeutic/preventive agents, yet their exact mechanisms of action on cell death and other inhibitory pathways are unknown [9,10,7,11,12].…”

Natural Sources of Tocotrienols: A Note on Absorption

“…Tocotrienols showed significant in vivo anticancer activity in breast cancer, pancreatic cancer and melanoma. Their anticancer activity is mediated by apoptosis, autophagy, and NFkB mediated pathways [48][49][50][51][52].…”

“…Caner is the most lethal disease in humans with very low survival rate [6,7] because of the cancer associated mutations in cells, and metastasis [8,9]. Vitamins and their sources have their key role as they have shown to have potent anticancer effect against various types of cancer with minimum toxicity [6,[10][11][12][13][14]. Several in vivo and human studies indicated the role of Vitamin E, especially γ-tocotrienol, being the potent anticancer agent against variety of cancers compared to other isoforms [15][16][17].…”

Advances in Genetic Improvement for Tocotrienol Production: A Review

“…Evidence suggests that some natural killer cells increased when tocotrienols were supplemented in mice. These contested MCF-7 breast cancer cells in humans (2). Research has also shown that oral administration of vitamin E supplements (tocotrienols and tocopherols) affects the human immune system, proliferation of spleen cells and lymphocytes (35).…”

“…Evans and Bishop (1922) were the first to discover vitamin E as a factor in the diet of rats that helped boost their reproduction. Vitamin E was isolated for the first time by Gladys Emerson at the University of California, Berkeley in 1935, followed by structural elucidation by Erhard Fernholz in 1938 and its first synthesis by a team of scientists headed by Paul Karrer in 1939 (2). The antioxidant activity of vitamin E prevents lipid peroxidation propagation and is beneficial for human health (3).…”