Despite significant advances in the diagnosis and treatment of cancer, the latter still remains a fatal disease due to the lack of prevention, early diagnosis, and effective drugs. Radiotherapy, chemotherapy, and surgery are not only expensive but produce a number of side effects that are detrimental to the patients' quality of life. Therefore, there is a great need to discover anti-cancer therapies that are specific to cancer cells and affordable, safe, and well tolerated by the patients. Vitamin E is a potential candidate due to its safety. Accumulating evidence on the anti-cancer potency of vitamin E has shifted the focus from tocopherols (TOCs) to tocotrienols (TTs). γ-TT and δ-TT have the highest anti-cancer activities and target common molecular pathways involved in the inhibition of the cell cycle, the induction of apoptosis and autophagy, and the inhibition of invasion, metastasis, and angiogenesis. Future directions should focus on further investigating how γ-TT and δ-TT (solely or in combination) induce anti-cancer molecular pathways when used in the presence of conventional chemotherapeutic drugs. These studies should be carried out in vitro, and promising results and combinations should then be assessed in in vivo experiments and finally in clinical trials. Finally, future research should focus on further evaluating the roles of γ-TT and δ-TT in the chemoprevention of cancer.
Keywords: Cancer; Caspase-independent programmed cell death; Tocotrienols; Vitamin E.
Induction of caspase-independent programmed cell death by vitamin E natural homologs and synthetic derivatives.Nutr Cancer. 2009;61(6):864-74. doi: 10.1080/01635580903285130. Nutr Cancer. 2009. PMID: 20155628
Anticancer properties of tocotrienols: A review of cellular mechanisms and molecular targets.J Cell Physiol. 2019 Feb;234(2):1147-1164. doi: 10.1002/jcp.27075. Epub 2018 Aug 1. J Cell Physiol. 2019. PMID: 30066964 Review.
Induction of DNA damage and caspase-independent programmed cell death by vitamin E.Nutr Cancer. 2012;64(1):136-52. doi: 10.1080/01635581.2012.630167. Epub 2011 Dec 15. Nutr Cancer. 2012. PMID: 22172208
Tocotrienols: The promising analogues of vitamin E for cancer therapeutics.Pharmacol Res. 2018 Apr;130:259-272. doi: 10.1016/j.phrs.2018.02.017. Epub 2018 Feb 27. Pharmacol Res. 2018. PMID: 29496592 Review.
δ-Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells.Cell Prolif. 2019 May;52(3):e12576. doi: 10.1111/cpr.12576. Epub 2019 Feb 4. Cell Prolif. 2019. PMID: 30719778 Free PMC article.