3,3'-Diindolylmethane Inhibits Pancreatic Cancer Cells

Scientists may have found a bioactive compound for the treatment of pancreatic cancer with no side effects, according to studies.

Pancreatic cancer is a chronic condition characterized by cell growth irregularly in the tissues of the pancreas.

According to statistics, every year, approximately, over 55,000 adults in the United States are diagnosed with pancreatic cancer, accounting to 3% of all cancers and 7% of all cancer deaths.

The survival rate of pancreatic cancer even diagnosed at the early is very low compared to other types of cancer. The 5-year survival rate at stage IA pancreatic cancer is only14%.

Researchers do not know what causes pancreatic cancer. They don't even know why people with the same health conditions in the same family, some are susceptible to pancreatic cancer, while others do not.

Most common risk factors of pancreatic cancer are similar to those of common cancers, including age, family history, gender, ethnicity, smoking, being overweight or obesity and certain medical conditions such as diabetes.

However, some researchers suggested that an unhealthy diet with high animal products such as the Western diet is associated with an increased risk of pancreatic cancer.


Dr. McCarty MF at the Pantox Laboratories, in the investigation of the insulin secretion as a determinant of pancreatic cancer risk, wrote, "In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion".

And, "There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention".

The results clearly indicated a reduced risk of diets associated with less consumption of animal products and high fruits and vegetables such as traditional and vegan diet.

3,3'-Diindolylmethane or DIM are phytochemicals derived from the digestion of indole-3-carbinol, belonging to the group of Indoles, found abundantly in broccoli, Brussels sprouts, cabbage, and kale, etc.

Researchers on finding a natural ingredient for the treatment of pancreatic cancer examined the function of dietary 3,3'-diindolylmethane (DIM) on the molecules of pancreatic cancer through the mechanistic underexpression of Krüppel-like factor 4 (KLF4) in pancreatic cancer.

Where Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor plays a critical role in the regulation of many cellular functions in both normal and neoplastic (benign or cancer) cells.

Injection of 3,3'-Diindolylmethane inhibited the overexpression of DNA methyltransferase 1 (DNMT1) in the promotion of cell cycle division, leading to the decreased KLF4 expression.

In other words, 3,3'-Diindolylmethane increased KLF4 expression in altering pancreatic cancer cells cycle progression by arresting the cells at the G2/M phase.


The findings indicated that DIM treatment caused significant inhibition of cell growth in vitro and tumorigenesis in animal models of pancreatic cancer.


Dr. Xie VK and colleagues said, "dysregulated KLF4 expression associated with poor differentiation of pancreatic cancer" and "dietary DIM causes differentiation and significant growth inhibition of pancreatic cancer cells".

In order to reveal more information about the effect of DIM against the progression pancreatic cancer, researchers investigated the overexpression of miR-221 in pancreatic cancer cell lines and tumor tissues compared to normal pancreatic duct epithelial cells and normal pancreas tissues.


Application of DIM exerted a significant effect in enhancing the transfection of miR-221 inhibitor in suppressing the proliferative capacity of pancreatic cancer cells accompanied by the activation of genes associated with tumor suppression.

Futhermore, injection of DIM alone or combined with isoflavone mixture (G2535), formulated 3,3'-diindolylmethane (BR-DIM), or synthetic curcumin analog (CDF) demonstrated a strong effect against the expression of miR-221 in pancreatic cancer cells, leading to the inhibition of cell proliferation and migration.

Dr. Sarkar S, the lead scientist wrote in the final report, "These results provide experimental evidence in support of the oncogenic role of miR-221 and also demonstrate the role of isoflavone, BR-DIM, and CDF as potential non-toxic agents that are capable of down-regulation of miR-221".

Taken altogether, 3,3'-Diindolylmethane derived from the I3C may be considered a supplement for the prevention and treatment of pancreatic cancer, pending to the confirmation of larger sample size and multicenter human study.

Intake of 3,3'-Diindolylmethane as a supplement should be taken with exceptional care to prevent acute liver toxicity.


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Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.

Sources
(1) DNA-Methyltransferase 1 Induces Dedifferentiation of Pancreatic Cancer Cells through Silencing of Krüppel-Like Factor 4 Expression by Xie VK1, Li Z2, Yan Y2, Jia Z2, Zuo X3, Ju Z4, Wang J4, Du J5, Xie D5, Xie K6, Wei D. (PubMed)
(2) Down-regulation of miR-221 inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN, p27(kip1), p57(kip2), and PUMA by Sarkar S1, Dubaybo H, Ali S, Goncalves P, Kollepara SL, Sethi S, Philip PA, Li Y. (PubMed)
(3) Insulin secretion as a determinant of pancreatic cancer risk.
McCarty MF. (PubMed)