Tocotrienol

What are tocotrienols?

● 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 infammaton.
● The primary reason tocotrienols may be benefcial 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.

  • Tocotrienols fight cancer by targeting multiple cell signalling 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 signalling 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.

    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

    Anticancerproperties of Tocotrienol are associated with targeting of multiple signaling pathways
    ● Tocotrienol inhibits VEGF-dependent tumor angiogenesis through downregulating the expression of both VEGF and VEGF receptor.
    ● It also inactivates the PI3/AKT signaling pathway by downregulating HER2/ErbB2 expression, which may associate with its suppressive effect on EMT.
    ● Tocotrienol inhibits cancer cell survival through suppression of NK-kappa B pathway. Downregulation of the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase appears to play an important role in this process.