The Study – Pancreatic Cancer

Pancreatic cancer is one of the most fatal cancers of all with the survival rate of just 2.9 – 5.6% after 5 years in case of distant or unknown stage and 28.9% as overall survival rate!

Fig. 1: The stage of cancer at diagnosis, refers to extent of a cancer in the body, determines treatment options and has a strong influence of the length of survival. If the cancer is found only in the part of the body where it started is localized (known as stage 1). If it has been observed to spread to a different part of the body, the stage is regional or distant. The earlier pancreatic cancer is diagnosed, the better are the rates of the survival in five years after being diagnosed. For pancreatic cancer, 10.3% are diagnosed at the local stage. The 5 – year survival for localized pancreatic cancer is 37.4%.

It has been estimated that there would be 56,770 new cases and estimated deaths would be 45,750. The lifetime risk of developing pancreatic cancer is approximately that 1.6% of men and women will be diagnosed with pancreatic cancer at some point during their lifetime, based on 2014 – 2016 data. In 2016 it self, there were an estimated 73,554 people living with pancreatic cancer in the United States. Pancreatic cancer is more common with increasing age and slightly more common in men than women. The number of new cases of pancreatic cancer was 12.9% per 100,000 men and women per year based on 2012 – 2016 cases.

Moreover most frightening feature of this cancer is that the population distribution of people who die of pancreatic cancer is similar to that of people who are diagnosed with this disease. It is also difficult to detect early, the average survival time from pancreatic cancer is low. Pancreatic cancer is the 3rd leading cause of cancer death in the United States.

In the pursuit to fight cancer, researchers have discovered Tocotrienolwhich is supposed to exhibit anti-cancer activities. Several studies have been conducted over Annatto based Tocotrienol(DeltaGold – Eannatto).  Several studies have been conducted on Tocotrienol for its effects against pancreatic cancer like, “Delta – Tocotrienol, a natural form of Vitamin E, inhibits pancreatic cancer stem – like cells and prevents pancreatic cancer metastasis” where the anti – cancer effects of Delta – Tocotrienol(DeltaGold – Eannatto)  against pancreatic cancer stem – cells were observed.

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.

Pancreatic Cancer
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 1 - Delta – Tocotrienol, a natural form of Vitamin E, inhibits pancreatic cancer stem – like cells and prevents pancreatic cancer metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is the most dangerous cancer, with a 5 – year survival rate of 8%. Approximately 25% of patients with PDAC have localized disease that is amenable to a curative approach with surgical resection combined with adjuvant chemotherapy. But, the prognosis of such patients is poor with a 5 – year survival rate of only 28.9%. It has been seen that pancreatic stem – likecells (metastasis – initiating cells) as a critical component of the mechanisms underlying PDAC relapse. Pancreatic CSCs express the cell surface markers CD44, CD24, and ES. They make up to 0.2% to 0.8% of human PDAC tumors. These CSCs have the ability to self – renew, generate differentiated progeny, are highly tumorigenic and metastatic, and are resistant to chemotherapies used to prevent PDAC relapse. Therefore, a new strategy targeting these CSCs may lead to prevention or delay in PDAC relapse.

It has been observed that among all 8 components of Vitamin E, Delta –Tocotrienol, a natural form of Vitamin E is the most potent Vitamin E against cancer cells. Studies have shown that, in contrast to Tocopherols, It has been observed that Tocotrienols have unique bioactive properties against cancer cells.

In this study it has been shown that Delta – Tocotrienol delays pancreatic cancer progression and improves the survival of genetically engineered mouse models of pancreatic oncogenesis (LSL – KRASG12D/PDX – 1 – Cre and LSL – KrasG12D/+; LSL – Trp 53R172H/+; Pdx – 1 – Cre [KPC]. It was further observed that Delta – Tocotrienol significantly inhibited metastasis and biomarkers of metastasis in the KPC model. Therefore, it was postulated that Delta – Tocotrienol might inhibit pancreatic CSCs and prevent metastases. It was observed that treatment with Delta – Tocotrienol markedly inhibited the viability, survival, and self – renewal of ancreatic CSCs. Moreover, Delta – Tocotrienol significantly inhibited biomarkers of process that underlie the mechanisms of metastasis such as migration, invasion, epithelial – to – mesenchymal transition (EMT), and angiogenesis. Finally, consistent with its in vitro activity, Delta – Tocotrienolhas been observed to significantly inhibit the growth and metastasis of human PDAC cells and pancreatic CSCs in orthotopicxenograftmouse models.

Results

  • Delta – Tocotrienol(DeltaGold – Eannatto) suppresses growth, self – renewal, and pluripotency factors and induces apoptosis in pancreatic cancer stem cells.
  • Delta – Tocotrienol(DeltaGold – Eannatto) inhibits migration and invasion of pancreatic cancer L3.6pl and MiaPaCa – 2 cells.
  • Delta – Tocotrienol(DeltaGold – Eannatto) inhibits epithelial – to – mesenchymal transition in pancreatic cancer cells and tumors.
  • Delta – Tocotrienol(DeltaGold – Eannatto) inhibits biomarkers of tumor angiogenesis and metastasis and induces apoptosis in pancreatic cancer cells and CSCs and in pancreatic tumors.
  • Delta – Tocotrienol(DeltaGold – Eannatto) inhibits pancreatic tumor growth and metastasis in mice.

Study 2 – In one other study conducted on pancreatic cancer, it was observed that when Delta – Tocotreinol or Gamma – Tocotrienol free from Tocopherol was used against the pancreatic cancer cells, the tumor growth was inhibited as shown in Fig. 2.

Pancreas Cancer

Fig. 2: When the cancerous pancreatic cell line (MIA PaCa 2 cells) was treated with Delta – Tocotrienol (Eannatto – DeltaGold), the tumor growth of significantly decreased as the days passed by with regular dosage as compared to mixture of Tocopherol and Tocotrienol.


In the same study on pancreatic cancer, around 200 – 3200 mg of Delta – Tocotrienol was used for 2 weeks and no toxicity was observed! And, it was also observed that cell apoptosis started at 200 mg/dose as shown in Fig. 3.

Cancer Studies

Fig. 3: A dose of 200 – 3200 mg per day was given for 2 weeks and as shown in the figure, 3200 mg/day was also safe without any toxic effects while the optimum dose was found to be 600 mg/day. Delta – Tocotrienol (Eannatto – DeltaGold) was observed to act against both Exocrine and Endocrine cancers.

Delta – Tocotrienol has also been observed to display its chemopeventive activity by inhibiting the progression of pancreatic intraepithelial neoplasm (PIN) in Kras transgenic mouse model via inhibition of Kras – driven pathways such as MEK/ERK, PI3K/Akt and Nf – kB and enhanced Bax and caspase -3 activities. Moreover, in vitro as well as in vivo settings have confirmed that Delta – Tocotrienol induced G1 cell cycle arrest by elevating nuclear accumulation of p27 (Kip1). Also, Delta – Tocotrienol(DeltaGold – Eannatto) also inhibited pancreatic cancer cell proliferation via suppression of ErbR2 and mevalonate pathway, and activation of caspase – dependent programmed cell death. Treatment of pancreatic cancer cells with Delta – Tocotrienols activated zinc finger transcription factor, EGR – 1 that enhanced the expression of Bax, consequently leading to apoptosis.

Summary

Why Tocotrienol?

  • Antioxidants, especially Tocotrienol was observed to exhibit anti-cancer activity against pancreatic cancer cells by lowering inflammation and oxidative stress as shown in Fig. 4.

    Clinical Study
    Fig. 4: 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 or formation of blood vessels in cancer cells promotes cancer cell growth to a very great extent. Tocotrienol is a master of anti-angiogenesis.

    Cancer Angiogenesis
Fig. 5: 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.
  • Apoptosis or programmed cell death is the process of elimination and death of cancer cells. Tocotrienol induces apoptosis in cancer cells by increasing endoplasmic reticulum stress and autophagy thus helping in killing cancer cells.
  • 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. According to several kinds of research, it has been proven that alpha, gamma, and delta Tocotrienols suppress the proliferation of cancer cells.
  • Chemoprevention and anti-cancer activities are some characteristic qualities of Tocotrienol.
  • 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.
  • Stem cells of the remaining 1% cancer cells which are never affected by chemotherapy and radiation and are travelling throughout the body which is also the main reason of reoccurrence of cancer even after those conventional treatments, has shown to be eliminated by Tocotrienol in the research. Just in last 5 years there are 6 studies which show that Tocotrienol target cancer stem cells as shown in Fig. 6.

    Stem Cells
Fig. 6: 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.

Dosage

  • A dose of 200 – 3200 mg per day was given for 2 weeks. 3200 mg/day was also found safe without any toxic effects observed while the optimum dose was found to be 600 mg/day.
  • Substances that complement Tocotrienol for cancer include Vitamins C, D, Selenium, B complex.

Why Tocotrienol and Not Tocopherol?

  • Tocotrienol the unappreciated Vitamin E: Since several decades, the majority of research has been focused on alpha-tocopherol whereas only 3% of the study has been conducted on Tocotrienol. However clinical studies have significantly proven that Tocotrienols display stronger anti-oxidant, anti-inflammatory, and chemopreventive activities than Tocopherol based Vitamin E.
  • 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.
  • Tocopherol in your food: The amount of antioxidants like Tocopherols required by your body is already present in our daily diet so we won’t get any benefit from Tocopherol supplementation.
  • Tocopherol, the enemy of Tocotrienol: Tocopherol interferes with the functioning of Tocotrienol as it attenuates 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 and target more cells.
  • Absorption: As compared to Tocopherols, Tocotrienols absorb better in the body and Tocopherols have been observed to prevent absorption of Tocotrienols.

    Tocotrienol Absorption

    Fig. 5:
    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.

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