Phytochemical 3,3'-Diindolylmethane Kills Pancreatic Cancer Cells in Vitro

Pancreatic cancer is a medical condition characterized by irregular cell growth in the tissue of the pancreas.

Most cases of pancreatic cancer start in the cell on the surface of the inner lining of the pancreatic tissue, before penetrating into the deeper layers to form a large and invasive tumor.

At the early stage, patients with pancreatic cancer may be asymptomatic. However, at the later stage, besides the common symptoms shared by all types of cancer such as unintended weight loss, loss of appetite, fatigue and gastrointestinal discomforts, patients with the condition may also experience localized symptoms such as internal bleeding and severe pain due to the oversize tumor which suppresses the nerve cells and blood vessels.

According to the statistic, in the US, every year, approximately 55,440 adults (29,200 men and 26,240 women) are diagnosed with pancreatic cancer.

The 5-year survival rate including all stages of people with pancreatic cancer is 8%, compared to 32% of cancer detected at an early stage.


The exact causes of pancreatic cancer are identified. However, epidemiological studies suggested that the increase in age, family history, race, gender, smoking, being obese or overweight and a medical condition such as diabetes is a most prevalent risk of the disease.


Some researchers indicated that genetic preposition may have a strong implication in the initiation of the onset of pancreatic cancer.


Dr. Alison P. Klein wrote, "These consist of high penetrance genes including BRCA2 or PALB2, to more common genetic variation associated with a modest increase risk of pancreatic cancer such as genetic variation at the ABO blood group locus".

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.

On finding a bioactive ingredient for the treatment of pancreatic cancer, researchers investigated the 3,3'-Diindolylmethane (DIM), ring-substituted DIMs and 1,1-bis(3'-indolyl)-1-(p-substitutedphenyl) methanes (C-DIMs) against the growth of Panc-1 and Panc-28 pancreatic cancer cells.


According to assays, Both DIM and DIM-C-pPhtBu induced pancreatic cancer cells. apoptosis observed by the increased endoplasmic reticulum (ER) staining and ER calcium release in Panc-1 cells.


Glucose-regulated protein 78, a protein in the endoplasmic reticulum in the cell played an important role in cellular adaptation and oncogenic survival also increased by the injection of both DIM and DIM-C-pPhtBu.

Furthermore, both DIM and DIM-C-pPhtBu. also exerted a significant activity against the pancreatic cancer cells through increasing the C/EBP homologous transcription factor in the regulation of cells apoptosis in response to cellular oxidative stress, similar to those of thapsigargin (Tg).


Moreover, DIM/DIM-C-pPhtBu- and Tg-induced ER stress in facilitating the pancreatic cancer cells death through cell death receptors and proteins associated with programming cell death.

Dr. the lead scientists after taking into account co and confounders wrote in the final report, "Activation of both receptor-dependent and receptor-independent (ER stress) pathways by DIM and DIM-C-pPhtBu in pancreatic cancer cells enhances the efficacy and potential clinical importance of these compounds for cancer chemotherapeutic applications".

Additionally, in order to reveal more information about DIM induced pancreatic cancer cells apoptosis, researchers analyzed the DIM effect by examing the process through multiple molecular assays.


According to the Western blot analysis, 3,3'-diindolylmethane (DIM) a chemopreventive agent, specifically its more bioavailable formulation, B-DIM, inhibited Par-4, in L3.6pl and Colo-357 pancreatic cancer cells at low doses (20 micromol/L).

At similar doses, DIM reduced cell viability and caused cell growth inhibition and apoptosis.

Also, pretreatment of DIM sensitized the cells to the cytotoxic action of chemotherapeutic drug gemcitabine.

In other words, DIM not only processed anti-pancreatic cancer cells proliferation and induced apoptosis but also promoted the chemotherapeutic drug cytotoxic activity against pancreatic cancer cells.

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

Intake of 3,3'-diindolylmethane in form of supplement should be taken with extreme care to prevent overdose 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) 3,3'-diindolylmethane (DIM) and its derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5,Abdelrahim M1, Newman K, Vanderlaag K, Samudio I, Safe S. (PubMed)
(2) Chemoprevention of pancreatic cancer: characterization of Par-4 and its modulation by 3,3' diindolylmethane (DIM) by Azmi AS1, Ahmad A, Banerjee S, Rangnekar VM, Mohammad RM, Sarkar FH. (PubMed)
(3) Genetic Susceptibility to Pancreatic Cancer by Alison P. Klein. (PMC)