Investigating the effects of Delta-Tocotrienol on Pancreatic Ductal Adenocarcinoma
SHOW SIGNIFICANT ANTICANCER PROPERTIES IN COLON CANCER CELLS
STIMULATE CASPASE-3 AND CASPASE-9 THUS INDUCING APOPTOSIS IN CANCER CELLS
Several research and studies have shown that Tocotrienols, especially the Delta and Gamma isoforms are natural bioactive against cancers as they delay their progression, help kill cancer cells, and suppress the growth of tumors. Delta-Tocotrienols have been observed to be one of the most potent antioxidant, anti-inflammatory, and anticancer agents.
Introduction to Pancreatic Cancer and Delta-Tocotrienol
Pancreatic adenocarcinoma is the most common type of pancreatic cancer and they usually start from the duct of the pancreas. It has been estimated that in the United States of America, in 2020 alone, 24,640 men and 22,410 women will be diagnosed with pancreatic cancer and around 47,050 people will die due to this disease. The worrisome fact regarding this cancer is that it is very difficult to diagnose because this cancer has no symptoms. If found at the early stages, then the tumor can removed and the life expectancy can be increased but since the prognosis isn’t easy, the cancer spreads quite fast and hence, the 5-year survival rate is just 9%. In this study, it has been shown that Delta-Tocotrienol is a natural bioactive against cancer, prevents metastases, and delays progression in transgenic mouse models of Pancreatic ductal adenocarcinoma. The striking feature of this study is that it has given the first evidence of Delta-Tocotrienol inhibits PDAC stem cells!
How does the Redox Derivative Tocotrienol fight Mesothelioma?
In this study, it has been observed that Delta-Tocotrienols prevents metastases and delays progression in transgenic mouse models of pancreatic ductal adenocarcinoma. Also, in this study, the first evidence of Delta-Tocotrienols selectively inhibiting PDAC stem-like cells was demonstrated. It was also observed that Delta-Tocotrienol inhibited the invasion, migration, and several biomarkers of epithelial to mesenchymal transition. Delta-Tocotrienol also suppressed angiogenesis, the process of formation of blood vessels in cancer cells, in the PDAC cells and tumors thus suppressing the tumor growth and the spread of cancer. In an orthotopic xenograft model of human pancreatic ductal adenocarcinoma cells, it was observed that Delta-Tocotrienols incredibly suppressed the growth and metastases of the PDAC human stem-like cells which were even resistant to the anti-cancer drug, gemcitabine! Hence, it can be concluded that, Delta-Tocotrienol can help in chemoprevention of PDAC metastases.
Reference for the Study in detail:
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29. [PubMed] [Google Scholar]
- Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK, Hruban RH. Recent progress in pancreatic cancer. CA Cancer J Clin. 2013;63:318–348. [PMC free article] [PubMed] [Google Scholar]
- Tempero MA, Malafa MP, Behrman SW, Benson AB, 3rd, Casper ES, Chiorean EG, Chung V, Cohen SJ, Czito B, Engebretson A, Feng M, Hawkins WG, Herman J, et al. Pancreatic adenocarcinoma, version 2.2014: featured updates to the NCCN guidelines. J Natl ComprCancNetw. 2014;12:1083–1093. [PubMed] [Google Scholar]
- Ischenko I, Petrenko O, Hayman MJ. Analysis of the tumor-initiating and metastatic capacity of PDX1-positive cells from the adult pancreas. Proc Natl Acad Sci U S A. 2014;111:3466–3471. [PMC free article] [PubMed] [Google Scholar]
- Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, Kamiyama M, Hruban RH, Eshleman JR, Nowak MA, Velculescu VE, Kinzler KW, Vogelstein B, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010;467:1114–1117. [PMC free article] [PubMed] [Google Scholar]
- Lee CJ, Dosch J, Simeone DM. Pancreatic cancer stem cells. J Clin Oncol. 2008;26:2806–2812. [PubMed] [Google Scholar]
- Lee CJ, Li C, Simeone DM. Human pancreatic cancer stem cells: implications for how we treat pancreatic cancer. Transl Oncol. 2008;1:14–18. [PMC free article] [PubMed] [Google Scholar]
- Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–1037. [PubMed] [Google Scholar]
- Abel EV, Simeone DM. Biology and clinical applications of pancreatic cancer stem cells. Gastroenterology. 2013;144:1241–1248. [PubMed] [Google Scholar]
- Husain K, Francois RA, Yamauchi T, Perez M, Sebti SM, Malafa MP. Vitamin E delta-tocotrienol augments the antitumor activity of gemcitabine and suppresses constitutive NF-kappaB activation in pancreatic cancer. Mol Cancer Ther. 2011;10:2363–2372. [PMC free article] [PubMed] [Google Scholar]
- Jiang Q. Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free RadicBiol Med. 2014;72:76–90. [PMC free article] [PubMed] [Google Scholar]
- Wong RS, Radhakrishnan AK. Tocotrienol research: past into present. Nutr Rev. 2012;70:483–490. [PubMed] [Google Scholar]
- Aggarwal BB, Sundaram C, Prasad S, Kannappan R. Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases. Biochemical pharmacology. 2010;80:1613–1631. [PMC free article] [PubMed] [Google Scholar]
- Ahsan H, Ahad A, Iqbal J, Siddiqui WA. Pharmacological potential of tocotrienols: a review. NutrMetab (Lond) 2014;11:52. [PMC free article] [PubMed] [Google Scholar]
- Peh HY, Tan WS, Liao W, Wong WS. Vitamin E therapy beyond cancer: Tocopherol versus tocotrienol. PharmacolTher. 2016;162:152–169. [PubMed] [Google Scholar]
- Husain K, Centeno BA, Chen DT, Hingorani SR, Sebti SM, Malafa MP. Vitamin E delta-tocotrienol prolongs survival in the LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC) transgenic mouse model of pancreatic cancer. Cancer Prev Res (Phila) 2013;6:1074–1083. [PMC free article] [PubMed] [Google Scholar]
- Husain K, Centeno BA, Chen DT, Fulp WJ, Perez M, Zhang Lee G, Luetteke N, Hingorani SR, Sebti SM, Malafa MP. Prolonged survival and delayed progression of pancreatic intraepithelial neoplasia in LSL-KrasG12D/+;Pdx-1-Cre mice by vitamin E delta-tocotrienol. Carcinogenesis. 2013;34:858–863. [PMC free article] [PubMed] [Google Scholar]
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 breast cancer cells, kindly refer to the reference link provided at the bottom of this abstract.