The Value of Tocotrienols in the Prevention and Treatment of Cancer

Abstract

Tocopherols and tocotrienols represent the 2 subgroups that make up the vitamin E family of compounds, but only tocotrienols display potent anticancer activity. Although in vitro experimental evidence has been very promising, oral supplementation of tocotrienols in animal and human studies has produced inconsistent results. However, recent studies have now clarified the reasons for these discrepancies observed between in vitro and in vivo studies. Oral absorption of tocotrienols into the circulation is mediated in large part by carrier transporter systems that display saturation and apparently down-regulation when exposed to high concentrations of tocotrienols. To circumvent these limitations in oral absorption of tocotrienols, investigators have developed novel prodrug derivatives and nanoparticle delivery systems that greatly enhance tocotrienol bioavailability and therapeutic responsiveness. Additional studies have also demonstrated that combined treatment of tocotrienols with other traditional chemotherapeutic agents results in a synergistic anticancer response, and this synergistic response was further enhanced when these agents were encapsulated in a nanoparticle delivery system. Taken together, these findings clarify the limitations of oral tocotrienol administration and provide novel alternative drug-delivery systems that circumvent these limitations and greatly enhance the therapeutic effectiveness of tocotrienols in the prevention and treatment of cancer.

Tocotrienol-rich mixture inhibits cell proliferation and induces apoptosis via down-regulation of the Notch-1/NF-κB pathways in NSCLC cells

“…For instance, miR-34a decreased the expression of Notch-1 and its downstream targets, including Hes-1, cyclin D1, Survivin, and Bcl-2, impairing Notch signaling, cell proliferation, and invasion and inducing apoptosis in NSCLC cells. 61 Epigenetic mechanism in Notch expression regulation has not been well studied. Therefore, it is very important to investigate the effect of TRMC on ligand-binding domains, ankyrin domains, and microRNAs as future directions.…”

“…Although in vitro experimental evidence has been very promising, oral supplementation of tocotrienols in animal and human studies has produced varying results. 61 Oral absorption of tocotrienols into the circulation is mediated by a carrier transporter system that displays saturation and downregulation when exposed to high concentrations of tocotrienols. 10,61 To compensate for these limitations in oral absorption of tocotrienols, investigators have developed new derivatives and nanoparticle delivery systems that significantly enhance tocotrienol bioavailability and, therefore, the therapeutic effects of tocotrienols on cancer.…”

“…61 Oral absorption of tocotrienols into the circulation is mediated by a carrier transporter system that displays saturation and downregulation when exposed to high concentrations of tocotrienols. 10,61 To compensate for these limitations in oral absorption of tocotrienols, investigators have developed new derivatives and nanoparticle delivery systems that significantly enhance tocotrienol bioavailability and, therefore, the therapeutic effects of tocotrienols on cancer. 61 In addition to bioavailability, timing and dosage are also concerns, and these factors will be different for cell cultures versus animals versus humans.…”

“…10,61 To compensate for these limitations in oral absorption of tocotrienols, investigators have developed new derivatives and nanoparticle delivery systems that significantly enhance tocotrienol bioavailability and, therefore, the therapeutic effects of tocotrienols on cancer. 61 In addition to bioavailability, timing and dosage are also concerns, and these factors will be different for cell cultures versus animals versus humans. Further experiments need to be conducted to investigate whether this capsule can show the same results in animals before it can be taken to a human trial, which is the ultimate goal.…”

Vitamin E Transporters in Cancer Therapy

“…The therapeutic potential of vitamin E isoforms in cancer therapy has been widely studied and thoroughly reviewed (16)(17)(18). Vitamin E members could be beneficial against a variety of cancer types, including breast, prostate, and colon through various possible mechanisms, including stimulation of wild-type p53 tumor suppressor gene, down-regulation of mutant p53 proteins, activation of heat shock proteins (HSPs), and possession an anti-angiogenic effect mediated by the blockage of transforming growth factor (TGF) (18)(19)(20)(21)(22)(23).…”