About every 3 minutes, one person in the United States of America is diagnosed with blood cancer. Around 176,200 people in the United States are expected to be diagnosed with leukemia, lymphoma or myeloma in 2019. Around 1,399,180 people in the USA are living with, or are in remission from blood cancer. In every 9 minutes, at least 1 person in the USA dies from a blood cancer. Around 156 people die each day or more than 6 people die every hour due to blood cancer in the USA.

For leukemia, around 61,780 people are expected to be diagnosed with leukemia in the USA.in 2019 and it is estimated that 399,967 people are already living with or are in remission from Leukemia in the USA. The 5 – year survival rate for leukemia is only 61.4% after 5 years as stated in the report by National Cancer Institute, USA! Very few patients survive for more than 10 years only due to the common reoccurrence of this cancer. Conventional treatment modalities for cancer including surgery, radiation, and chemotherapy have failed to eradicate cancer entirely.

From 2011 to 2015, leukemia was the 6th most common cause of cancer deaths in both men and women in the USA. Moreover, Leukemia is diagnosed 10 times more often diagnosed in adults than children. Everyday around 150 – 179 Americans are diagnosed with leukemia and 67 lose their battle against it. Leukemia is the most common cancer in Hispanic children and adolescents. 5 – year survival rate is around 3% to 4% lower for Hispanics than that of non – Hispanic whites.

To bring a better solution against such deadly disease, researchers and doctors have discovered natural anti-oxidants in the form of Annatto based Tocotrienol (Eannatto – DeltaGold) which can also be used with other chemotherapeutic drugs that exhibit strong anti-cancer activities and one of these kinds of research is “Gamma-Tocotrienol and Simvastatin Synergistically Induce Cytotoxicity In Leukemia Cell Lines, K-562 and HL-60” where it was observed that Gamma-Tocotrienol, an isoform of Vitamin E, and simvastatin, a cholesterol lowering drug exhibit synergy in induction of cytotoxicityin K-562 and HL-60 leukemia cell lines. Eannatto, has successfully harvested Annatto for Tocotrienols rich in Delta – Tocotrienol and Gamma – Tocotrienol to help Leukemia patients throughout the globe in their fight against blood cancer.

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.

Study – Gamma-Tocotrienol and Simvastatin Synergistically Induce Cytotoxicity In Leukemia Cell Lines, K-562 and HL-60.

Statins and Tocotrienols regulate the cholesterol biosynthesis – pathway by inhibiting the 3-hydroxy-3- methylglutaryl coenzyme A (HMG – CoA) reductase. Tocotrienols modulate the 3-hydroxy-3- methylglutaryl coenzyme A (HMG – CoA) reductase by post – transcriptional down – regulation. Also, Tocotrienols contain a farnesol moiety in their side – chain that triggers degradation of HMG-CoA reductase. These effects lead to suppression of cell proliferation, cell cycle arrest, and apoptosis. Several studies have shown that statins have suppressive effects in in vitro experiments on acute myelocytic leukemia cell lines. Since both statins & Gamma – Tocotrienols (Eannatto – DeltaGold) are associated with decrease in cholesterol biosynthesis, we hypothesized that if the cytotoxicity of these drugs on cancer cells is related to impaired biosynthesis of cholesterol, combination of them may synergize in cytotoxicity on leukemic cells.

K-562 and HL-60 leukemia cells were grown in Iscove’s Modified Dulbecco’s medium with penicillin or streptomycin, 10% fetal bovine serum and 20% fetal bovine serum were added respectively. K-562 and HL-60 leukemia cells were seeded in 96 well plates, were grown overnight, and treated for 24 hours, 48 hours and 72 hours with simvastatin in concentrations of 1 µM, 2 µM, 4 µM, and 5 µM; Gamma – Tocotrienol (Eannatto – DeltaGold) in concentrations of 20 µM, 40 µM, and 80 µM; and a combination of the two drugs in the same concentrations. For the 24 hour dose, cells were seeded at a density of 5000/well and for 48 and 72 hour doses, at 3500/well. Following the treatment, MTS/PMS reagent (Promega, Madison, WI), [3 – (4, 5 – dimethylthiazol – 2 – yl) – 5 – (3 – carboxymethoxyphenyl) – 2 – (4 – sulfophenyl) – 2H – tetrazolium, inner salt] mixed with and an electron coupling reagent (phenazine methosulfate), was added at 40 µg/well and incubated at 37°C for 2 hours. The solubilized formazan crystals at 450 nm were measured as an indicator of cytotoxicity. The presence of Adenosine Triphosphate (ATP) as an indicator of cell viability was measured with the CellTiter Glo® assay (Promega). Cells were again seeded, grown overnight, and dosed as mentioned above.  Following treatment, the assay was conducted as specified by the manufacturer.

Both Simvastatin and Gamma – Tocotrienol (Eannatto – DeltaGold) induced cytotoxicity in K-562 and HL-60 cell lines by the MTS and Cell Titer Glo Assays.  The IC50 at 72 hour incubation were as follows 1) HL-60: simvastatin – 16.543 uM, gamma tocotrienol – 36.297 uM;  2) K-562: simvastatin – 5.235 uM, gamma tocotrienol – 34.947 uM.  We used CompuSyn to calculate the IC50.  When combined, simvastatin and Gamma – Tocotrienol (Eannatto – DeltaGold) exhibit synergy at lower concentrations when examined by isobologram analysis.

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%.

Fig. 3: In a study, it was observed in mice cells, that Delta – Tocotrienol inhibited the formation of blood vessels in cancer cells (Anti – Angiogenesis) while Tocopherol completely failed on such grounds. Delta-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.

Dosage

Why Tocotrienol and Not Tocopherol?

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

Note:

  1. To read studies in detail, follow the references and links given.
  2. The dosages given must not be taken as the advice of a medical practitioner. Consult your physician for the optimum dosage to be consumed.