Vitamin E Eannatto δ-tocotrienol Suppresses Skin Cancers like Melanoma

Investigating the effects of Vitamin E Delta-Tocotrienol on malignant melanoma cells i.e. Skin Cancer
The following abstract is taken from a published study and is explained in simple terms to help you understand better. For deeper and technical insights regarding the action of Tocotrienols on human skin cancer cells, kindly refer to the reference link provided at the bottom of this abstract.



Introduction to Melanoma or Skin Cancer and Delta-Tocotrienol
Malignant melanoma is the deadliest skin cancer and it’s faster-growing cancer in terms of incidence rate in humans, with a 2.6% increase in the number of melanoma cancers over the last decade. Although, melanomas are curable in the early stages the prognosis of melanomas in the late stages is still very poor. The first treatment options include alkylating agents like dacarbazine and temozolomide and cytokines like interleukin-2 and interferon- α. However, there are serious side effects and melanoma develops resistance easily against these drugs. Hence, a potent substitute was needed to suppress this cancer.
In this study, the effects of Delta-Tocotrienol, on the tumor and cell growth of melanoma were investigated. The involvement of endoplasmic reticulum stress and the role of Delta-Tocotrienol in suppressing melanoma. The study and the experiments were carried out on human melanoma cells and nude mice xenografts.
How does the Delta-Tocotrienol fight Skin cancer?
It was observed in the study that, Delta-Tocotrienol significantly induces apoptosis on the BLM, and A275, human melanoma cell lines. The mechanism involved the intrinsic apoptosis pathway and surprisingly, the normal human skin cells weren’t affected by Delta-Tocotrienol! The results showed that Delta-Tocotrienol suppressed the tumor growth through activation of the ATF4, CHOP, IRE1α, PERK, p-eIF2α, and caspase-4 ER stress-related branches.
In vivo studies, experiments were performed in nude mice bearing A375 xenografts. It was observed that Delta-Tocotrienol reduced the tumor volume and also, the tumor mass! Moreover, even tumor progression was incredibly delayed and suppressed by Delta-Tocotrienols.
To conclude the study, the data suggested that Delta-Tocotrienols exerted proapoptotic activity on melanoma skin cancer cells through the activation of the ER-related pathways which can increase the possibility of Delta-Tocotrienol emerging as an effective option for a novel chemopreventive agent for melanoma!
Reference for the Study in detail:
2. Higgins, H. W., 2nd, Lee, K. C., Galan, A. & Leffell, D. J. Melanoma in situ: Part I. Epidemiology, screening, and clinical features. J Am Acad Dermatol 73, 181–190 (2015).
3. Jilaveanu, L. B., Aziz, S. A. & Kluger, H. M. Chemotherapy and biologic therapies for melanoma: do they work? Clin Dermatol 27, 614–625 (2009).
4.Vujic, I. et al. Mutant NRASQ61 shares signaling similarities across various cancer types–potential implications for future therapies. Oncotarget 5, 7936–7944 (2014).
5.Niezgoda, A., Niezgoda, P. & Czajkowski, R. Novel Approaches to Treatment of Advanced Melanoma: A Review on Targeted Therapy and Immunotherapy. Biomed Res Int 2015, 851387 (2015).
6. Larkin, J., Hodi, F. S. & Wolchok, J. D. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med 373, 1270–1271 (2015).
7.Hao, M. et al. Advances in targeted therapy for unresectable melanoma: new drugs and combinations. Cancer Lett 359, 1–8 (2015).
8.Swinney, D. C. & Anthony, J. How were new medicines discovered? Nat Rev Drug Discov 10, 507–519 (2011).
9.Hosseini, A. & Ghorbani, A. Cancer therapy with phytochemicals: evidence from clinical studies. Avicenna J Phytomed 5, 84–97 (2015).
10. Scarpa, E. S. & Ninfali, P. Phytochemicals as Innovative Therapeutic Tools against Cancer Stem Cells. Int J Mol Sci 16, 15727–15742 (2015).
11.Shanmugam, M. K., Kannaiyan, R. & Sethi, G. Targeting cell signaling and apoptotic pathways by dietary agents: role in the prevention and treatment of cancer. Nutr Cancer 63, 161–17 (2011).
12. Tete, S. et al. Nutrition and cancer prevention. Int J Immunopathol Pharmacol 25, 573–581 (2012).
13.Ahsan, H., Ahad, A., Iqbal, J. & Siddiqui, W. A. Pharmacological potential of tocotrienols: a review. Nutr Metab (Lond) 11, 52 (2014).
14.Peh, H. Y., Daniel Tan, W. S., Liao, W. & Fred Wong, W. S. Vitamin E therapy beyond cancer: tocopherol versus tocotrienol. Pharmacol Ther, doi: 10.1016/j.pharmthera.2015.12.003 (2015).
15. Kline, K., Lawson, K. A., Yu, W. & Sanders, B. G. Vitamin E, and cancer. Vitam Horm 76, 435–461 (2007).
16.Yano, T., Sato, A., Sekine, M., Virgona, N. & Ota, M. Redox-inactive analogue of tocotrienol as a potential anti-cancer agent. Anticancer Agents Med Chem 13, 496–501 (2013).
17.Nesaretnam, K. & Meganathan, P. Tocotrienols: inflammation and cancer. Ann N Y Acad Sci 1229, 18–22 (2011).
18.Kannappan, R., Gupta, S. C., Kim, J. H. & Aggarwal, B. B. Tocotrienols fight cancer by targeting multiple cell signaling pathways. Genes Nutr 7, 43–52 (2012).
19.Ling, M. T., Luk, S. U., Al-Ejeh, F. & Khanna, K. K. Tocotrienol as a potential anticancer agent. Carcinogenesis 33, 233–239 (2012).
20. Lim, S. W., Loh, H. S., Ting, K. N., Bradshaw, T. D. & Zeenathul, N. A. Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells. BMC Complement Altern Med 14, 469 (2014).
21. Wang, M. & Kaufman, R. J. Protein misfolding in the endoplasmic reticulum as a conduit to human disease. Nature 529, 326–335 (2016).
22. Schonthal, A. H. Pharmacological targeting of endoplasmic reticulum stress signaling in cancer. Biochem Pharmacol 85, 653–666 (2013).
23. Foufelle, F. & Fromenty, B. Role of endoplasmic reticulum stress in drug-induced toxicity. Pharmacol Res Perspect 4, e00211 (2016).
24. Halperin, L., Jung, J. & Michalak, M. The many functions of the endoplasmic reticulum chaperones and folding enzymes. IUBMB Life 66, 318–326 (2014).
25. Parmar, V. M. & Schroder, M. Sensing endoplasmic reticulum stress. Adv Exp Med Biol 738, 153–168 (2012).
26. Sano, R. & Reed, J. C. ER stress-induced cell death mechanisms. Biochim Biophys Acta 1833, 3460–3470 (2013).
27. Hiramatsu, N., Chiang, W. C., Kurt, T. D., Sigurdson, C. J. & Lin, J. H. Multiple Mechanisms of Unfolded Protein Response-Induced Cell Death. Am J Pathol 185, 1800–1808 (2015).

Leave a Reply

Your email address will not be published. Required fields are marked *

Add to cart