Anti-Angiogenesis as Strategy for Cancer Inhibition

The tocotrienol (or TCT) group—together with tocopherols—compose the vitamin E family. Natural tocotrienols exist in four different forms or isomers, named alpha-, beta-, gamma- and delta- tocotrienol, each which contain different number of methyl groups on the chromanol ring. The major structural difference from tocopherol is through its unsaturated side chain that has three double bonds in its farnesyl isoprenoid tail. All of the isomers have been demonstrated to have some level of antioxidant activity due to the donating hydrogen atom from the hydroxyl group on the chromanol ring that might reduce free radicals in the body. However, some of the isomers have been further investigated through a number of clinical and non-clinical studies for other biological activities. The investigations have shown promise in pre-clinical and clinical applications that include cancer treatment and cholestrol control, benefits that may be lesser or even lacking in the more commonly used synthetic alpha-tocopherol as discussed later.

Tocotrienols are named by analogy to tocopherols (from Greek words meaning to bear a pregnancy . but with this word changed to include the chemical difference that tocotrienols are trienes, meaning that they share identical structure with the tocopherols except for the addition of three double bonds to their side chains.

Tocotrienols and breast cancer

A study showed that tocotrienols are the components of vitamin E responsible for growth inhibition in human breast cancer cells in vitro as well as in vivo through estrogen-independent mechanisms. Tocotrienols can also affect cell homeostasis, possibly independently of their antioxidant activity. Anti-cancer effects of α- and γ-tocotrienol have been reported, although δ-tocotrienol was verified to be the most effective tocotrienol in inducing apoptosis (cell death) in estrogen-responsive and estrogen-nonresponsive human breast cancer cells. A daily dose of 30 - 50 mg mixture of α- and γ-tocotrienols can reduce breast cancer risk, and a treatment plan for breast cancer should use higher dosage.

Tocotrienols and prostate cancer

Investigation of the antiproliferative effect of tocotrienols in PC3 and LNCaP prostate cancer cells suggests that the transformation of vitamin E to CEHC is mostly a detoxification mechanism, useful to maintain the malignant properties of prostate cancer cells.[4] However, recent research suggested that γ-tocotrienol was most potent in suppressing prostate cancer cell proliferation, and that the antiproliferative effect of γ-tocotrienol act through multiple-signalling pathways (NF-B, EGF-R and Id family proteins). In addition, the same study demonstrated the anti-invasion and chemosensitisation effect of γ-tocotrienol against PCa cells.