Tocotrienol and cancer metastasis

Abstract

Tumor metastasis involves some of the most complex and dynamic processes in cancer, often leading to poor quality of life and inevitable death. The search for therapeutic compounds and treatment strategies to prevent and/or manage metastasis is the ultimate challenge to fight cancer. In the past two decades, research focus on vitamin E has had a shift from saturated tocopherols to unsaturated tocotrienols (T3). Despite sharing structural similarities with tocopherols, T3 strive to gain scientific prominence due to their anti-cancer effects. Recent studies have shed some light on the anti-metastatic properties of T3. In this review, the roles of T3 in each step of the metastatic process are discussed. During the invasion process, signaling pathways that regulate the extracellular matrix and tumor cell motility have been reported to be modulated by T3. Although studies on T3 and tumor cell migration are fairly limited, they were shown to play a vital role in the suppression of angiogenesis. Furthermore, the anti-inflammatory effect of T3 could be highly promising in the regulation of tumor microenvironment, which is crucial in supporting tumor growth in distant organs.

Targeting melanoma stem cells with the Vitamin E derivative δ-tocotrienol

“…TTs (specifically, γ-TT and δ-TT) were widely reported to be associated with significant health benefits in different chronic diseases, based on their neuroprotective, cholesterol-lowering, antioxidant and antiinflammatory activites 27 , 28 . TTs were also shown to possess antitumor activity by suppressing cancer cell proliferation and by increasing the sensitivity of tumor cells to chemotherapeutic agents 29 , 30 . We recently reported that δ-TT exerts a significant proapoptotic activity in human cutaneous melanoma cells (while sparing normal melanocytes), independently on their genetic mutations, by triggering the endoplasmic reticulum (ER) stress prodeath pathways 31 .…”

Utilization of Vitamin E Analogs to Protect Normal Tissues While Enhancing Antitumor Effects

“…In addition to cancer prevention, researchers are exploring the therapeutic role of tocotrienols in cancers (79–82). Here we present a selection of studies published in this area.…”

Protective Effect of Palm Oil-Derived Tocotrienol-Rich Fraction Against Retinal Neurodegenerative Changes in Rats with Streptozotocin-Induced Diabetic Retinopathy

“…Antioxidants have been shown to be of therapeutic benefit in oxidative stress-induced diseases, including DR [18,19]. Since TRF has shown potent antioxidant effects in several human and animal studies [20][21][22][23], it may be of potential therapeutic value against DR. Additionally, some in vitro and in vivo studies have also shown that TRF produces anti-cancer effects due to its anti-angiogenic properties [24]. The anti-angiogenic properties of TRF have been attributed to its ability to suppress several signaling pathways, such as Ras-Raf-MEK-ERK and Fyn/HIF-1a pathways, leading to downregulation of VEGF expression [25].…”