Tocotrienol

Cancer Therapy

Tocotrienol cancer therapy

Tocotrienols are a group of chemicals that are part of the vitamin E family. So far, research has uncovered numerous benefits associated with tocotrienols. Vitamin E is an essential nutrient that contains tocotrienols and tocopherols. Both tocotrienols and tocopherols have similar chemical structures. The difference between tocotrienols and tocopherols is that tocotrienols have double bonds. Tocotrienols are often found in natural sources such as palm or rice brain oil. People take tocotrienols by mouth for aging, Alzheimer's disease, clogged arteries, cancer, diabetes, a genetic disorder called familial dysautonomia, high cholesterol, kidney failure, and stroke. People apply tocotrienols to the skin for buns, hair growth, and scars.

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, α-, δ-, and γ-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 ERβ, but not for ERα. Moreover, we have demonstrated that specific tocotrienols increase ERβ translocation into the nucleus which, in turn, activates the expression of estrogen-responsive genes (MIC-1, EGR-1 and Cathepsin D) in breast cancer cells only expressing ERβ cells (MDA-MB-231) and in cells expressing both ER isoforms (MCF-7). The binding of specific tocotrienol forms to ERβ 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

Tocotrienols fight cancer by targeting multiple cell signaling pathways

Cancer cells are distinguished by several distinct characteristics, such as self-sufficiency in growth signal, resistance to growth inhibition, limitless replicative potential, evasion of apoptosis, sustained angiogenesis, and tissue invasion and metastasis. Tumor cells acquire these properties due to the dysregulation of multiple genes and associated cell signaling pathways, most of which are linked to inflammation. For that reason, rationally designed drugs that target a single gene product are unlikely to be of use in preventing or treating cancer. Moreover, targeted drugs can cause serious and even life-threatening side effects. Therefore, there is an urgent need for safe and effective promiscuous (multitargeted) drugs. “Mother Nature” produces numerous such compounds that regulate multiple cell signaling pathways, are cost effective, exhibit low toxicity, and are readily available. One among these is tocotrienol, a member of the vitamin E family, which has exhibited anticancer properties. This review summarizes data from in vitro and in vivo studies of the effects of tocotrienol on nuclear factor-κB, signal transducer and activator of transcription (STAT) 3, death receptors, apoptosis, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), hypoxia-inducible factor (HIF) 1, growth factor receptor kinases, and angiogenic pathways.

What are tocotrienols?

Both tocotrienols and tocopherols may be referred to as vitamin E. Vitamin E is an antioxidant, which means that it helps to neutralize free radicals. Free radicals are chemicals linked to a host of health issues, including skin aging, cancer, and numerous diseases. Free radicals can also cause chronic inflammation. The primary reason tocotrienols may be beneficial is because of their antioxidant properties. Cereal grains tend to be rich in tocotrienols.

Good sources include:
❯ rice bran
❯ oats
❯ barley
❯ rye
❯ crude palm oil

How does it work?

Tocotrienols exist in four different forms: alpha-, beta-, gamma-, and delta-tocotrienols. Tocotrienols seem to have many different effects in the body. Tocotrienols might lower cholesterol levels and provide heart health benefits. Tocotrienols also seem to benefit people with a genetic disorder called familial dysautonomia by increasing levels of a certain protein in blood cells.

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