**1. Introduction**

Vitamin E is a fat-soluble antioxidant that comprises two major classes, the tocopherols and the tocotrienols. Structurally, tocotrienols are similar to tocopherols in which both isomers of vitamin E consist of chromanol core ring and polyprenyl side chain. However, the difference lies in the fact that the polyprenyl side chain of tocotrienols has three unsaturated bonds at 3′, 7′ and 11′ positions, which are connected to carbon number 2 of the chiral centre [1] (**Figure 1**). Similar to tocopherols, tocotrienols also have four different isomers, which is determined by the number and position of the methyl groups on the chromanol ring. They are α-tocotrienol, β-tocotrienol, γ-tocotrienol 7 and δ-tocotrienol [2] (**Figure 2**). Tocotrienol discovery was first annotated in 1961 and was described in greater detail in 1964, in which it was identified from the latex of the rubber plant, *Hevea brasiliensis*, in 1964 [3]. Tocotrienols first received critical attention in the early 1980s when it was first reported that they were able to lower cholesterol levels *in vitro* (hepatocytes of chicken and mouse) as well as *in vivo* (animal

#### **Figure 1.**

*The chemical structure of tocopherols and tocotrienols.*

#### **Figure 2.**

*Chemical structures of the four isoforms of tocotrienols.*

experimentation using chicken and mouse). In the early 1990s, the anti-cancer properties of tocotrienols were also reported [3].

The concentrations of tocotrienols in various plants have been well-characterized and described. Palm oil, rice bran, wheat germ oil, coconut oil and annatto seeds have all been ascertained to contain tocotrienols in varying concentrations [4, 5]. Palm oil contains 0.66% α-tocotrienol, 0.019% β-tocotrienol, 0.71% γ-tocotrienol, 0.31% δ-tocotrienol. Rice bran contains 0.43% α-tocotrienol,

#### *Palm Oil Tocotrienols in Cancer Chemoprevention and Treatment DOI: http://dx.doi.org/10.5772/intechopen.98199*

0.08% β-tocotrienol, 0.63% γ-tocotrienol, 0.04% δ-tocotrienol. Wheat germ oil 1.94% α-tocotrienol and 0.05% δ-tocotrienol, whereas in coconut oil there is 0.2% α-tocotrienol, 0.04% γ-tocotrienol, 0.76% δ-tocotrienol [6, 7]. In annatto seeds, most of the tocotrienol is δ-tocotrienol with a content ranging from 140 to 147 mg/100 g of dry seed [8]. Tocotrienols are the predominant vitamin E found in palm oil, rice bran and annatto seeds [9]. Out of all the various sources of tocotrienols, palm oil is the most sustainable, most easily available, and one of the richest sources of tocotrienols, i.e., the vitamin E isomer most extensively used in Asian countries as a health supplement. The various vitamin E components found in palm oil include α-tocopherol, α-tocotrienol, γ-tocotrienol, and δ-tocotrienol. The tocotrienol-rich fraction of palm oil (TRF) consists of 23.54% α-tocotrienol, 43.16% γ-tocotrienol, 9.83% δ-tocotrienol, and 23.5% α-tocopherol and is extracted from palm oil post-esterification and following distillation, crystallization, and chromatography processes [6, 7].

As a potent antioxidant, tocotrienols exert a variety of beneficial biological and health effects. Tocotrienols have been shown to have cardioprotective and anti-ageing effects [10]. Studies have also suggested that tocotrienols prevent atherosclerosis and improved blood vessel function in diabetics [10]. In an animal experimental model, the deleterious effects of the strong oxidant ferric nitrilotriacetate on bones were prevented by the administration of tocotrienols [11]. Previous studies had shown that tocotrienols prevented hepatotoxicity due to exposure to harmful chemicals and prevented alterations in the acidity of stomach content due to the increase in gastrin secretion [12, 13]. Tocotrienol, in combination with ascorbic acid, had been shown to increase the levels of neutrophils and lymphocytes, thus strengthening the immunity of the body [14]. In patients with rheumatoid arthritis, tocotrienols administration was associated with a reduction in joint inflammation [15].

Tocotrienols are thought to treat and prevent cancer by suppressing the secretion of angiogenic factors from carcinogenic cells, and by acting as adjuvant drugs to improve the efficacy of existing anticarcinogenic drugs due to their immunemodulating properties [16]. Delta-tocotrienol has specifically been suggested to be a viable alternative treatment for brain and lung malignancies [17]. There have been suggestions that the tocotrienols, either alone or in combination with other bioactive compounds, is beneficial for the prevention and treatment of cancer patients [18, 19]. This review will therefore focus on the role of tocotrienols in cancer chemoprevention and cancer therapeutic management. Many studies have associated the antioxidant properties of vitamin E with the alleviation of carcinogenesis [20–22]. Therefore, this review will also discuss the antioxidative properties of vitamin E (which includes the tocotrienols) in the treatment of cancers. The antioxidant activity associated with vitamin E (tocopherols and tocotrienols) are thought to be the most effective free radical scavengers, which could prevent the generation of reactive oxygen species (ROS) molecules. It has been suggested that tocopherols and tocotrienols prevented living cells from becoming malignant by quashing the attack initiated by free radicals [23, 24]. In addition to their antioxidant properties, the anticancer effects of tocotrienols had also been shown to be related to their interaction with different intracellular signalling pathways. Therefore, this review will also elaborate upon the various pathways affected by tocotrienols in different types of cancer.
