The Study – Glioblastoma
Glioblastoma or Brain cancer is one of the rarest cancers but with the highest mortality rates! This year, it has been estimated that 23,820 adults which include 13,410 men and 10,410 women in the United States will be diagnosed with primary cancerous tumors of the brain and spinal cord. Brain tumors account for 85% to 90% of all the primary CNS tumors and also,it has been estimated that about 3,720 children under the age of 15 will be diagnosed with a brain or CNS tumor this year.Brain and other nervous system cancers are the 10th most leading causes of death for men and women. It is estimated that 17,760 adults which include 9,910 men and 7,850 women will die from primary cancerous brain and CNS tumors this year.The 5 – year survival rate for people suffering from a cancerous brain or CNS tumor is approximately 34% for men and 36% for women.
In India it has been found that the median survival rates are in the range of 9–12 months and 2-year survival rates are in the range of 8%–12%.The incidence of central nervous system (CNS) tumors in India ranges from 5 to 10 per 100,000 people with an increasing trend and accounts for 2% of the total malignancies.Although the survival rate of patients with GBM has improved with recent advancements in treatment, the prognosis remains generally poor. Conventional treatments for Glioblastoma like surgery, radiation, and chemotherapy have failed to completely eliminate cancer and help evade its reoccurrence. Henceforth, researchers have discovered Tocotrienol(Eannatto – DeltaGold)from Annatto which is 100% pure and they have conducted several studies like “Gamma-tocotrienol and hydroxy-chavicol synergistically inhibit growth and induces apoptosis of human glioma cells” in which they have discovered natural anti-oxidants in the form of Annatto based Tocotrienol exhibit strong anti-cancer activities and moreover, Eannatto has successfully harvested Annatto for Tocotrienols to deliver antioxidants with maximum percentage of Alpha, Delta and Gamma Tocotrienols to every corner of the world and provide maximum health benefits.
Fig. 1: In the graph, as you can see, R & D on Tocotrienol has increased exponentially over the years in all fields while research on Tocopherols has decreased. Whether it is cancer, Cardiovascular diseases (CVD), Diabetes, Anti – Oxidant activities or others, in all fields research on Tocotrienol has not only gained pace but quant as well.
In Glioblastoma, the potential of Delta – Tocotrienol (Eannatto – DeltaGold) is elucidated by uts ability to induce marked cytotoxicity in SF – 295 gliobklastoma cells in vitro. More notably, all the isoforms of Tocotrienol have been observed to induce apoptosis in glioblastoma in vitro by activating caspase – 8 and enhancing mitochondrial cytochrome c (cyt. c) release due to loss of mitochondrial membrane integrity.
Study - Gamma-tocotrienol and hydroxy-chavicol synergistically inhibit growth and induces apoptosis of human glioma cells.
Gamma – Tocotrienol(Eannatto – DeltaGold), an isomer of vitamin E and hydroxyl – chavicol(HC), a major bioactive compound in Piper betle, has been observed to possess anti – carcinogenic properties by modulating different cellular signaling events. One possible strategy to overcome multi – drug resistance and high toxic doses of treatment is by applying combinational therapy especially using natural bio – actives in cancer treatment.
In this study, the interaction of Gamma – Tocotrienol(Eannatto – DeltaGold) and hydroxyl – chavicol and its mode of cell death on glioma cell lines was investigated. Gamma – Tocotrienol(Eannatto – DeltaGold)or hydroxyl – chavicol alone and in combination were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) by [3 – (4,5 – dimethylthiazol – 2 –yl) – 5 – (3 – carboxymethoxy – phenyl) – 2 – (4 – sulfophenyl) – 2H – tetrazolium, inner salt] MTS assay. The interactions of each combination were evaluated by using the combination index obtained from an isobologram.
Individually, Gamma – Tocotrienol(Eannatto – DeltaGold) or hydroxyl – chavicoldisplayed growth inhibitory effects against glioma cancer cell lines at concentration values ranging from 42 – 100 μg/ml of Gamma – Tocotrienoland 75 – 119 μg/ml of hydroxyl – chavicol. However, the combination of sub – lethal doses of Gamma – Tocotrienol(Eannatto – DeltaGold) + hydroxyl – chavicol dramatically enhanced the inhibition of glioma cancer cell proliferation and exhibited a strong synergistic effect on 1321N1 with CI of 0.55, and CI = 0.54 for SW1783. While in LN18 cells, moderate synergistic interaction of GTT + HC was observed with CI value of 0.73. Exposure of grade II, III and IV cells to combined treatments for 24 hours led to increased apoptosis as determined by annexin-V FITC/PI staining and caspase-3 apoptosis assay, showing caspase-3 activation of 27%, 7.1% and 79% respectively.
In conclusion, combined treatments with sub – effective doses of Gamma – Tocotrienol(Eannatto – DeltaGold)and hydroxyl – chavicolresulted in synergistic inhibition of cell proliferation through the induction of apoptosis of human glioma cells in vitro.
Fig. 3: In a study, it was observed in mice cells, thatTocotrienol inhibited the formation of blood vessels in cancer cells (Anti – Angiogenesis) while Tocopherol completely failed on such grounds. Tocotrienol was also observed to induce apoptosis in the mice cancer cells.
Fig. 4: About 1% of cancer cells are Cancer Stem Cells (CSC) which keep circulating in your body even after nailing the cancer through chemo. It has been observed that Gamma – Tocotrienol and Delta – Tocotrienol, both specifically target CSC.
Fig. 5: In the first graph, it can be observed that Tocotrienol uptake is maximum when Alpha – Tocopherol concentration is 0 but as the concentration of Alpha – Tocopherol increases, the concentration of uptake of Tocotrienol decreases. While, in the 2nd graph it can be observed that as the concentration of Alpha – Tocopherol increases in the dosage of Tocotrienol, the apoptosis induction property of Tocotrienol was suffered and cancer kill was compromised.
Fig. 6: The 2nd pie chart represents Palm Tocotrienol rich fraction with 32% Alpha – Tocopherol which was given to people and when the Alpha – Tocopherol was removed then it was represented by the 1st pie chart with 0.3% Alpha – Tocopherol which was then given to people. In the graph, the hollow bar represents the Tocotrienol with Tocopherol which reduced the concentrations of Alpha, Gamma and Delta Tocotrienol in the body but when Tocopherol was removed from the dosage (Solid grey bars in graph), the concentrations of Alpha, Gamma and Delta – Tocotrienol significantly increased.
References
To read studies in detail, follow the references and links given.
The dosages given must not be taken as the advice of a medical practitioner. Consult your physician for the optimum dosage to be consumed.
In India it has been found that the median survival rates are in the range of 9–12 months and 2-year survival rates are in the range of 8%–12%.The incidence of central nervous system (CNS) tumors in India ranges from 5 to 10 per 100,000 people with an increasing trend and accounts for 2% of the total malignancies.Although the survival rate of patients with GBM has improved with recent advancements in treatment, the prognosis remains generally poor. Conventional treatments for Glioblastoma like surgery, radiation, and chemotherapy have failed to completely eliminate cancer and help evade its reoccurrence. Henceforth, researchers have discovered Tocotrienol(Eannatto – DeltaGold)from Annatto which is 100% pure and they have conducted several studies like “Gamma-tocotrienol and hydroxy-chavicol synergistically inhibit growth and induces apoptosis of human glioma cells” in which they have discovered natural anti-oxidants in the form of Annatto based Tocotrienol exhibit strong anti-cancer activities and moreover, Eannatto has successfully harvested Annatto for Tocotrienols to deliver antioxidants with maximum percentage of Alpha, Delta and Gamma Tocotrienols to every corner of the world and provide maximum health benefits.
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.
Fig. 1: In the graph, as you can see, R & D on Tocotrienol has increased exponentially over the years in all fields while research on Tocopherols has decreased. Whether it is cancer, Cardiovascular diseases (CVD), Diabetes, Anti – Oxidant activities or others, in all fields research on Tocotrienol has not only gained pace but quant as well.
In Glioblastoma, the potential of Delta – Tocotrienol (Eannatto – DeltaGold) is elucidated by uts ability to induce marked cytotoxicity in SF – 295 gliobklastoma cells in vitro. More notably, all the isoforms of Tocotrienol have been observed to induce apoptosis in glioblastoma in vitro by activating caspase – 8 and enhancing mitochondrial cytochrome c (cyt. c) release due to loss of mitochondrial membrane integrity.
Study - Gamma-tocotrienol and hydroxy-chavicol synergistically inhibit growth and induces apoptosis of human glioma cells.
Gamma – Tocotrienol(Eannatto – DeltaGold), an isomer of vitamin E and hydroxyl – chavicol(HC), a major bioactive compound in Piper betle, has been observed to possess anti – carcinogenic properties by modulating different cellular signaling events. One possible strategy to overcome multi – drug resistance and high toxic doses of treatment is by applying combinational therapy especially using natural bio – actives in cancer treatment.
In this study, the interaction of Gamma – Tocotrienol(Eannatto – DeltaGold) and hydroxyl – chavicol and its mode of cell death on glioma cell lines was investigated. Gamma – Tocotrienol(Eannatto – DeltaGold)or hydroxyl – chavicol alone and in combination were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) by [3 – (4,5 – dimethylthiazol – 2 –yl) – 5 – (3 – carboxymethoxy – phenyl) – 2 – (4 – sulfophenyl) – 2H – tetrazolium, inner salt] MTS assay. The interactions of each combination were evaluated by using the combination index obtained from an isobologram.
Individually, Gamma – Tocotrienol(Eannatto – DeltaGold) or hydroxyl – chavicoldisplayed growth inhibitory effects against glioma cancer cell lines at concentration values ranging from 42 – 100 μg/ml of Gamma – Tocotrienoland 75 – 119 μg/ml of hydroxyl – chavicol. However, the combination of sub – lethal doses of Gamma – Tocotrienol(Eannatto – DeltaGold) + hydroxyl – chavicol dramatically enhanced the inhibition of glioma cancer cell proliferation and exhibited a strong synergistic effect on 1321N1 with CI of 0.55, and CI = 0.54 for SW1783. While in LN18 cells, moderate synergistic interaction of GTT + HC was observed with CI value of 0.73. Exposure of grade II, III and IV cells to combined treatments for 24 hours led to increased apoptosis as determined by annexin-V FITC/PI staining and caspase-3 apoptosis assay, showing caspase-3 activation of 27%, 7.1% and 79% respectively.
In conclusion, combined treatments with sub – effective doses of Gamma – Tocotrienol(Eannatto – DeltaGold)and hydroxyl – chavicolresulted in synergistic inhibition of cell proliferation through the induction of apoptosis of human glioma cells in vitro.
Summary
Why Tocotrienol?
Fig. 2: In the study conducted by Dr. Qureshi, he saw that at 250 mg of Tocotrienols, the endogenous anti-oxidant, TAS (represented with grey colour) increased, while the C-reactive protein (CRP) dropped by 40%, oxidized fat (MDA) dropped by 34% and Total Anti-oxidant increased by 22%.
Why Tocotrienol?
- Antioxidants, especially Tocotrienol was observed to exhibit anti-cancer activity against brain cancer cells cells by lowering inflammation and oxidative stress as shown in Fig. 2.
Fig. 2: In the study conducted by Dr. Qureshi, he saw that at 250 mg of Tocotrienols, the endogenous anti-oxidant, TAS (represented with grey colour) increased, while the C-reactive protein (CRP) dropped by 40%, oxidized fat (MDA) dropped by 34% and Total Anti-oxidant increased by 22%.
- Angiogenesis which is the process of formation of blood vessels in cancer cells like in your brain cancer. Tocotrienol promotes cancer cell death to a very great extent and good results of anti-angiogenesis property of Tocotrienols have been observed against brain cancer cells in the study.Studies have also demonstrated that Tocotrienol hindered hypoxia-induced VEGF and IL-8 overexpression and by lowering HIF-1 alpha, thus consequently inhibiting angiogenesis in cancer cells.
Fig. 3: In a study, it was observed in mice cells, thatTocotrienol inhibited the formation of blood vessels in cancer cells (Anti – Angiogenesis) while Tocopherol completely failed on such grounds. Tocotrienol was also observed to induce apoptosis in the mice cancer cells.
- Apoptosis or programmed cell death is the process of elimination and death of cancer cells. All the isoforms of Tocotrienol have been observed to induce apoptosis in Glioblastoma in vitro by activating caspase-8 and enhancing mitochondrial cytochrome release due to loss of mitochondrial membrane integrity.
- Cell Proliferation is the process by which cancer cells copy their DNA and divide into two cancer cells during mitosis and rapidly multiply into more cancer cells. Gamma-Tocotrienol has been observed to inhibit cell proliferation through the induction of apoptosis of human glioma cells in vitro.
- Chemoprevention and anti-cancer activity against Glioblastoma have been observed in Tocotrienols.
- Chemosensitization is the combination of Tocotrienol with several chemotherapeutic drugs such as celecoxib, statins or dietary components such as curcumin, polyphenols, etc. which effectively sensitize the cancer cells. In a study, combined treatments with sub-effective doses of Gamma-Tocotrienol and Hydroxyl-Chavicol have been observed to inhibit growth and induce apoptosis of human glioma cells.
- TRF or Tocotrienol Rich Fractions trapped in transferrin bearing vesicles were observed to remarkably enhance the cytotoxic activity of TRF by more than a 100 folds in Glioblastoma T98G cells by improving the uptake of TRF.
- 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.
Fig. 4: About 1% of cancer cells are Cancer Stem Cells (CSC) which keep circulating in your body even after nailing the cancer through chemo. It has been observed that Gamma – Tocotrienol and Delta – Tocotrienol, both specifically target CSC.
- 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 several kinds of research, it has been observed that approximately 900 mg/day of Tocotrienols have been used to treat colon cancer cells with no adverse effects and productive results.
- Substances that complement Tocotrienol for cancer include Vitamins C, D, Selenium, B complex.
- 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.
- 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.
- 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.
Fig. 5: In the first graph, it can be observed that Tocotrienol uptake is maximum when Alpha – Tocopherol concentration is 0 but as the concentration of Alpha – Tocopherol increases, the concentration of uptake of Tocotrienol decreases. While, in the 2nd graph it can be observed that as the concentration of Alpha – Tocopherol increases in the dosage of Tocotrienol, the apoptosis induction property of Tocotrienol was suffered and cancer kill was compromised.
- 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 Efor Cancer Therapeutics
https://doi.org/10.1016/j.phrs.2018.02.017 - Gamma-tocotrienol and hydroxy-chavicol synergistically inhibits growth and induces apoptosis of human glioma cells by Abdul Rahman A, Jamal AR, Harun R, Mohd. Mokhtar N, Wan Ngah WZ.
https://www.ncbi.nlm.nih.gov/pubmed/24980711 - Cancer.net: Brain Tumor: Statistics
https://www.cancer.net/cancer-types/brain-tumor/statistics - Indian data on central nervous tumors: A summary of published work
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991137/
To read studies in detail, follow the references and links given.
The dosages given must not be taken as the advice of a medical practitioner. Consult your physician for the optimum dosage to be consumed.
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