**1. Introduction**

Breast cancer is the second leading cause of death in women, and it originates from malignant breast cancer cells displaying unregulated growth to produce a tumor mass [1, 2]. Several cellular mechanisms are dysregulated in breast tumor cells, including the canonical Wnt and Hedgehog signaling pathways, which play an important role in promoting oncogenic proliferation, survival, motility, invasion, and epithelial-to-mesenchymal transition (EMT) [3]. Although these events are complex and poorly understood, recent findings show that specialized cell membrane microdomains known as lipid rafts are involved in mediating membrane receptor activation and signal transduction. Lipid rafts are solid platforms in the plasma membrane that consist of cholesterol and sphingolipids. Lipid rafts are essential for cellular signaling by recruiting transmembrane receptors with adaptor and signaling proteins from non-rafts to the raft area of the cell membrane [4–6]. In the case of canonical Wnt and Hedgehog signaling, low-density lipoprotein receptor-related protein 6 (LRP6) and patched (PTCH2), the main receptors for activation of these signaling pathways, were shown to be primarily located in the lipid raft microdomain [7–9]. Lipid rafts have been shown to be essential for Hedgehog signal transduction [10]. γ-Tocotrienol is a natural vitamin E isoform that displays potent anticancer activities [11–13]. Previous reports have clearly shown that γ-tocotrienol exerts antiproliferative and apoptotic activity against neoplastic mammary epithelial cells at treatment doses that had little or no effect on normal cell growth and viability [14, 15]. The anticancer effects of γ-tocotrienol appear to be mediated through a variety of intracellular signaling mechanism [16–18]. Recently, γ-tocotrienol was found to disrupt lipid raft integrity and attenuation of receptor signaling transduction [19]. This chapter will focus of experimental evidence demonstrating γ-tocotrienol reversal of EMT is mediated through the inhibition of the canonical Wnt and Hedgehog signaling pathways.

or tocopherol. Tocotrienols differ from tocopherols only in that they contain an unsaturated, whereas tocopherols contain a saturated phytyl tail. **Figure 1** shows the chemical structures

**Tocopherol Tocotrienols Dietary oil α α γ δ Total tocotrienol**

γ-Tocotrienol Reversal of Epithelial-to-Mesenchymal Transition in Human Breast Cancer Cells…

http://dx.doi.org/10.5772/intechopen.78273

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Palm 152 205 439 94 738 Rice brain 324 236 349 – 586 Wheat germ 133 26 – – 26 Coconut 5 5 1 19 25 Palm-kernel 12 21 – – 21 Coco butter 11 2 2 Corn 112 – – – 0 Cottonseed 389 – – – 0 Peanut 130 – – – 0 Olive 51 – – – 0 Safflower 387 – – – 0 Soybean 101 – – – 0 Sunflower 487 – – – 0

Interestingly, numerous studies have shown that tocotrienols, but not tocopherols, have selective antiproliferative and apoptotic effects against various forms of breast cancer, while have little effect on normal mammary epithelial cell growth or function [14, 15, 25]. The anticancer

of different isoforms of tocotrienols.

**Table 1.** Vitamin E levels (mg/L) in common dietary oils [21].

**Figure 1.** General chemical structure of the different tocotrienols isoforms.
