Tocotrienols fight cancer by targeting multiple cell signaling pathways

Abstract

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-jB, 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.

A Combination of δ-Tocotrienol and Ferulic Acid Synergistically Inhibits Telomerase Activity in DLD-1 Human Colorectal Adenocarcinoma Cells

“…T3 has been shown to decrease the proliferation of cancer cells derived from breast, colon, liver, lung, stomach, skin, pancreas, prostate, blood, and cervix (6). The growth suppressive effects of T3 are attributed to apoptosis and G1 cell cycle arrest.…”

Advances in Genetic Improvement for Tocotrienol Production: A Review

“…The different forms of tocotrienols possess different properties and perform different functions in the human body (see Table 2); a-tocotrienol can prevent inducible neurodegeneration (8) and was effective in treating cerebral ischemia, while g-and d-tocotrienol have anticancer properties (34). Oral supplements of tocotrienol protect against stroke and protect neurons against any neurotoxicity (33).…”

“…Among the various compounds found in whole grains, tocotrienol has the highest anticancer activity (34). This property is now the focus of preclinical and clinical trials.…”

A Brief Journey of Tocotrienols as Anticancer Agents

“…These chromans are more aqueous soluble and excreted in urine [11]. Successful in vitro and in vivo studies are available to prove the anticancer activities of tocotrienols in wide range of cancers and other health disorders [6,[12][13][14][15][16]. Studies are also being conducted to advantage of alternative formulation (Figure 3) types to enhance bioavailability of the drugs [17][18][19].…”