It’s been observed that one in every 3 cancers diagnosed is a skin cancer. The main factor that leads to the occurrence of skin cancer is exposure to ultraviolet radiation, usually from the sun and more recently from artificial tanning sunbeds. Although UV rays make up for a very small portion of the sun’s rays, they are the major cause of the sun’s damaging effects on the skin. Ultraviolet rays damage the DNA of skin cells. Skin cancers usually start when this damage affects the DNA of genes that control skin cell growth. Small quantities of UV are essential for the production of vitamin D, yet overexposure may lead to acute and chronic health effects on the skin, eye and immune system.

Research on skin cells has shown that the vitamin E family members especially Tocotrienols (Eannatto – DeltaGold) works on both the genetic and protein levels to produce firmer, fairer skin and larger muscles. Tocotrienols (Eannatto – DeltaGold) have been observed to work at the cellular level – the smallest unit of living beings. Tocotrienols (Eannatto – DeltaGold) have also been observed to help reduce damage from ultraviolet rays. And at the same time, they help reduce free radicals created by UV radiation. Several studies have been conducted on Tocotrienols (Eannatto – DeltaGold) where they have been observed to protect skin tissues against UV radiation. One such study, “Diet – derived and topically applied Tocotrienols accumulate in skin and protect the tissue against ultraviolet light – induced oxidative stress” demonstrated the protective effect of Tocotrienols for the skin cells. Another study, “Targeting melanoma stem cells with the Vitamin E derivative Delta – Tocotrienol” showed that Delta – Tocotrienol (Eannatto – DeltaGold) targeted and destroyed melanoma stem cells which are usually not targeted by the conventional cancer treatments like chemotherapies and radiation.

Since the past several decades, Tocotrienols have shown great applications in dermatology for their protection against photosensitivity. Tocotrienols have also been observed to be very effective against skin cancer. Delta – Tocotrienol (DeltaGold – Eannatto) and its peroxy dimer have been found to effectively impede proliferation of melanoma cells. Also, Delta – Tocotrienol (DeltaGold – Eannatto) has been observed to induce G1 cell cycle arrest in A2058 and A375 human melanoma cells, via down – regulating CDK – 4 and activating caspase – 3. Furthermore, research and studies have shown that Gamma – Tocotrienol (DeltaGold – Eannatto) induce apoptosis in melanoma cells via suppression of Nf – kB , EGFR , Id family proteins and JNK signaling pathway. The anti-cancer effect of Delta – Tocotrienol (DeltaGold – Eannatto) has also been elucidated by its ability to induce apoptosis via ER stress in melanoma both in vitro and in vivo. Also, an in vivo study, it was showed that intravenous administration of Alpha – Tocotrienol entrapped in transferrin – bearing vesicles caused complete tumor eradication in 60% of B16-F10 melanoma tumor and extended the survival of mice. Also, Gamma – Tocotrienol (DeltaGold – Eannatto) treatment was observed to halt cell invasion in human melanoma through inhibition of mesenchymal markers and restoration of E-cadherin and Gamma – Catenin. ERK signaling pathway, which in turn down-regulated melanogenesis-related proteins such as proteins, TYRP-1 and TYRP-2. Moreover, it was also showed that tocomin enhanced the degradation of melanosomes in melanoma cells by up – regulating endosome docking/fusion proteins including syntaxin7, vacuolar protein sorting – associated protein Vps16, Vps33, and Vps41. Collectively, these reports have shown the growing potential of Tocotrienol for skin cancer treatment. Moreover, Tocotrienols (Eannatto – DeltaGold) has been observed to possess anti-ageing effects on the skin, including preventing wrinkle formation, protecting against ultra-violet (UV) rays, and have a whitening effect.

Most research in the past 50 – 60 years has been focused on Tocopherols and 50% of all the research in last 30 years has been done on Tocotrienols in last 5 years. Half of the Tocotrienol research ever published has been published in last 10 years as shown in Fig. 1. Each day it is becoming increasingly understood that Tocotienols (especially Eannatto – DeltaGold) are the right form of Vitamin E. Well in excess of 100 studies and clinical trials have shown the surprising benefits of Tocotrienols – without any known side effects.

Study 1 – Targeting melanoma stem cells with the Vitamin E derivative Delta – Tocotrienol.

The prognosis of metastatic melanoma is quite poor, due to the development of drug resistance of this disease. Cancer stem cells (CSCs) have been estimated to play a major role in this mechanism, contributing to disease relapse. CSCs were first characterized in melanoma cell lines. It was observed that A375 (but not BLM) cells were able to form melanospheres and show CSCs traits which is the expression of the pluripotency markers SOX2 and KLF4, higher invasiveness and tumor formation capability in vivo with respect to parental adherent cells. It was also showed that a subpopulation of auto – fluorescent cells expressing the ABCG2 stem cell marker were present in the A375 spheroid culture. On the basis of these data, it was investigated whether δ-TT might target melanoma CSCs. We demonstrated that melanoma cells escaping the antitumor activity of Delta – Tocotrienol (Eannatto – DeltaGold) are completely devoid of the ability to form melanospheres. In contrast, cells that were observed to escape vemurafenib treatment showed a higher ability to form melanospheres than control cells. Delta – Tocotrienol (Eannatto – DeltaGold) was also observed to induce disaggregation of A375 melanospheres and were also observed to reduce the spheroidogenic ability of sphere – derived cells, reducing the expression of the ABCG2 marker. These data demonstrated that Delta – Tocotrienol (Eannatto – DeltaGold) exerts its antitumor activity by targeting the CSC subpopulation of A375 melanoma cells and it also might represent a novel chemopreventive/therapeutic strategy against melanoma.

Study 2 – Diet – derived and topically applied Tocotrienols accumulate in skin and protect the tissue against ultraviolet light – induced oxidative stress.

To evaluate the tissue – specific distribution of lipophilic antioxidants including vitamin E isoforms, the Tocotrienols and Tocopherols and oxidised and reduced coenzyme Q (ubiquinone and ubiquinol), a sensitive procedure was developed using gradient HPLC with both electrochemical- and ultraviolet – detection. A unique distribution of these antioxidants in hairless mouse tissues was found, suggesting that their distribution may be dependent upon selective mechanisms for maintaining antioxidant defenses. Ubiquinol – 9 was found highest in the kidneys (81 ± 29 nmol/g) and in the liver (42 ± 16 nmol/g), while the highest ubiquinone – 9 concentrations were found in the kidneys (301 ± 123 nmol/g) and in the heart (244 ± 22 nmol/g). Liver was observed to contain nearly identical amounts of each ubiquinol – 9 (41 ± 16 nmol/g) and ubiquinone – 9 (46 ± 18 nmol/g). These mice tissues were fed a commercial chow diet containing Alpha – Tocopherol (30 ± 6 mg/kg diet), Gamma – Tocopherol (10 ± 1), Alpha – Tocotrienol (3.1 ± 0.7) and Gamma – Tocotrienol (Eannatto – DeltaGold) (7.4 ± 1.7). Of the vitamin E forms, brain contained only Alpha – Tocopherol (5.4 ± 0.1 nmol/g; 99.8%) and no detectable Tocotrienols. In other tissues, the Alpha – Tocopherol content was higher (20 nmol/g), while each of the other forms represented about 1 % of the total (Gamma – Tocopherol 0.2 to 0.4 nmol/g, Alpha – Tocotrienol 0.1, Gamma – Tocotrienol 0.2). Remarkably, skin was observed to contain nearly 15% Tocotrienols and 1% Gamma – Tocopherol. The unique distribution of Tocotrienols in skin suggested that they might have superior protection against environment stressors like UV rays. Therefore, the penetration of topically applied Tocotrienol enriched fraction of palm oil, (TRF) and vitamin E homologue concentrations before and after exposure of skin to UV – light was assessed. 20 μL of 5% TRF in polyethylene glycol-400 (PEG) was applied to 2 skin sites of the mice tissue and 20 μL PEG to the 2 other sites. After 2 hours, the skin was washed and half of the sites exposed to UV-irradiation using a solar simulator (2.8 mW/cm2 for 29 min). The vitamin E content of hairless mouse skin was Alpha –Tocopherol (9.0 ± 1.0 nmol/g skin), Gamma – Tocopherol (0.44 ± 0.03), Alpha – Tocotrienol (0.48 ± 0.07), Gamma – Tocotrienol (.92 ± 0.03). Topical TRF enriched skin vitamin E: Alpha – Tocopherol (201 ± 70 nmol/g skin), Gamma – Tocopherol (37 ± 15), Alpha – Tocotrienol (53 ± 25), and Gamma – Tocotrienol (50 ± 24). After UV-irradiation, concentrations of all vitamin E homologues from both treatment areas decreased significantly (p<0.01), but the TRF – treated skin contained vitamin E at concentrations 7- to 30-fold higher than control values. These results provided provocative clues on the uptake and regulation of tissue lipophilic antioxidants. The unique distribution of these antioxidant substances suggests their distribution may be dependent upon tissue-specific selective mechanisms.

Summary

Antioxidants, especially Tocotrienol was observed to exhibit anti-cancer activity against skin cancer cells by lowering inflammation and oxidative stress as shown in Fig. 2.

Angiogenesis which is the process of formation of blood vessels in cancer cells like in your skin cancer promotes cancer cell death to a very great extent. Studies have also demonstrated that Delta-Tocotrienol hindered hypoxia-induced VEGF and IL-8 overexpression and by lowering HIF-1 alpha, thus consequently inhibiting angiogenesis in cancer cells.

Apoptosis is the programmed cell death which leads to the death of cancer cells. According to the study, Tocotrienol was found to induce apoptosis in colon cancer cells in vitro and in vivo by downregulating NF-kB and its regulated gene products. Delta – Tocotrienol ( DeltaGold – Eannatto ) has been observed to cause cell death in aberrant melanoma and moreover it was observed that Delta – Tocotrienol ( DeltaGold – Eannatto ) did not affect healthy cells.

is the programmed cell death which leads to the death of cancer cells. According to the study, Tocotrienol was found to induce apoptosis in colon cancer cells in vitro and in vivo by downregulating NF-kB and its regulated gene products. Delta – Tocotrienol ( ) has been observed to cause cell death in aberrant melanoma and moreover it was observed that Delta – Tocotrienol ( ) did not affect healthy cells. Paraptosis is a type of programmed cell death distinct from apoptosis which features cytoplasmic vacuolation independent of Caspase activation and inhibition, and lack of apoptotic morphology. According to the research, it was observed that Delta-Tocotrienol induced paraptosis-like cell death in cancer cells.

is a type of programmed cell death distinct from apoptosis which features cytoplasmic vacuolation independent of Caspase activation and inhibition, and lack of apoptotic morphology. According to the research, it was observed that Delta-Tocotrienol induced paraptosis-like cell death in cancer cells. Cell Proliferation is the process by which cancer cells copy their DNA and divide into several cancer cells during mitosis which leads to the spreading of cancer. Tocotrienol has been observed to impede the proliferation of cancer cells

is the process by which cancer cells copy their DNA and divide into several cancer cells during mitosis which leads to the spreading of cancer. Tocotrienol has been observed to impede the proliferation of cancer cells Chemoprevention and anti-cancer activity against colon cancer have been observed in Tocotrienols.

and anti-cancer activity against colon cancer have been observed in Tocotrienols. Cancer stem cell death has been observed by the action of Tocotrienols especially Delta – Tocotrienols (DeltaGold – Eannatto). Even after chemotherapies, radiation and surgeries, there are stem cells of those cancerous tissues left revolving in your body which can lead to your cancer coming back. Henceforth, their death is very necessary and Tocotrienols have been observed to kill cancer stem cells. Tocotrienols have also been observed to exert anti – tumor activity against melanoma by targeting cancer stem cells.

Tumor nutrition can also be obstructed by Tocotrienol as they may well work on dual antitumor mechanisms that include the removal of the vital nutrient to tumor lifeline. In a melanoma study, Delta – Tocotrienols ( DeltaGold – Eannatto ) have been observed to reduce tumor volume and tumor mass in mice and significantly delay tumor progression.

can also be obstructed by Tocotrienol as they may well work on dual antitumor mechanisms that include the removal of the vital nutrient to tumor lifeline. In a melanoma study, Delta – Tocotrienols ( ) have been observed to reduce tumor volume and tumor mass in mice and significantly delay tumor progression. Free Radicals have been observed to be reduced by Tocotrienols which are created by UV – radiation.

have been observed to be reduced by Tocotrienols which are created by UV – radiation. Growth of Melanoma have been observed to be restricted by Delta and Gamma – Tocotrienol ( DeltaGold – Eannatto ) in studies conducted at the University of Wisconsin/Madison and at the Texas Woman’s University on cell cultures and animals.

have been observed to be restricted by Delta and Gamma – Tocotrienol ( ) in studies conducted at the University of Wisconsin/Madison and at the Texas Woman’s University on cell cultures and animals. Hyperpigmentation has been observed to be reduced by the effect of Delta – Tocotrienol ( DeltaGold – Eannatto ).

has been observed to be reduced by the effect of Delta – Tocotrienol ( ). Skin Damage and Healing of Wounds has also been observed to be repaired by the effect of Tocotrienols.

has also been observed to be repaired by the effect of Tocotrienols. Skin Pigmentation and Blemishes have been observed to be reduced by Delta – and Gamma – Tocotrienol ( DeltaGold – Eannatto ) by inhibiting Melanin Synthesis.

have been observed to be reduced by Delta – and Gamma – Tocotrienol ( ) by inhibiting Melanin Synthesis. SPF value of Delta – Tocotrienol (DeltaGold – Eannatto) has been found to be 5.5.

Dosage

In several kinds of research, it has been observed that approximately 900 mg/day of Tocotrienols have been used to treat skin cancer cells with no adverse effects and productive results.

Substances that complement Tocotrienol for cancer include Vitamins C, D, Selenium, B complex.

Why Tocotrienol and Not Tocopherol?

Tocopherol, the enemy of Tocotrienol : In the studies, Tocopherol was observed to interfere in the functioning of Tocotrienol! Tocopherol has been observed to attenuate cancer inhibition, inhibits absorption, reduces adipose storage, and compromises cholesterol and triglyceride reduction.

: In the studies, Tocopherol was observed to interfere in the functioning of Tocotrienol! Tocopherol has been observed to attenuate cancer inhibition, inhibits absorption, reduces adipose storage, and compromises cholesterol and triglyceride reduction. Tocotrienol, the protector of State: Tocotrienol has more mobility than Tocopherol due to its small structure so it can cover a larger area targeting more number of colon cancer cells.

Tocotrienol has more mobility than Tocopherol due to its small structure so it can cover a larger area targeting more number of colon cancer cells. Small structure and less molecular weight: The higher anti-oxidant activity of Tocotrienols is due to their small structure and less molecular weight which assist in their integration of the cell, unlike Tocopherols.

Absorption: As compared to Tocopherols, Tocotrienols absorb better in the body and Tocopherols have been observed to prevent absorption of Tocotrienols.

References

Tocotrienols: Latest Cancer Research in Vitamin E by Barrie Tan, Ph.D., and Anne M.Trias, MS.

Tocotrienols: The Promising Analogues of Vitamin E for Cancer Therapeutics

https://doi.org/10.1016/j.phrs.2018.02.017

https://doi.org/10.1016/j.phrs.2018.02.017 Targeting melanoma stem cells with the Vitamin E derivative δ-tocotrienol.

https://www.ncbi.nlm.nih.gov/pubmed/29330434

https://www.ncbi.nlm.nih.gov/pubmed/29330434 Diet-derived and topically applied tocotrienols accumulate in skin and protect the tissue against ultraviolet light-induced oxidative stress.

https://www.ncbi.nlm.nih.gov/pubmed/24394657

https://www.ncbi.nlm.nih.gov/pubmed/24394657 Want smooth, white skin and larger muscles? Think tocotrienols

https://www.thestar.com.my/lifestyle/health/2014/12/07/want-smooth-white-skin-and-larger-muscles-think-tocotrienols/

https://www.thestar.com.my/lifestyle/health/2014/12/07/want-smooth-white-skin-and-larger-muscles-think-tocotrienols/ WHO: Global Health Observatory Data: Ultraviolet radiation

https://www.who.int/gho/phe/ultraviolet_radiation/en/

https://www.who.int/gho/phe/ultraviolet_radiation/en/ org: What is Ultraviolet (UV) Radiation?

https://www.cancer.org/cancer/skin-cancer/prevention-and-early-detection/what-is-uv-radiation.html

https://www.cancer.org/cancer/skin-cancer/prevention-and-early-detection/what-is-uv-radiation.html The Truth About Vitamin E: The Secret to Thriving with Annatto Tocotrienols by Dr. Barrie Tan.

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