Phytochemical 3,3'-Diindolylmethane, the Bioactive Compound Which Kills Gastric Cancer Cells

By Kyle J. Norton


Gastric cancer is a chronic condition characterized by irregular cells growth in the tissues of the stomach.

Most cases of gastric cancer start in the cells on the surface of the inner lining of stomach tissue.
Due to the small size at the early stage, gastric cancer is asymptomatic.

However, at the later stage, after penetrating into the deeper layers of the stomach, the cancer cell may travel a distance away to infect other healthy tissues and organs, leading to secondary metastasis.

At this stage, most patients with gastric cancer may experience symptoms of severe abdominal pain caused by the suppressing of the oversize tumor on the nerve cells, or vague discomfort in the abdomen, usually above the navel, particularly heartburn and indigestion, accompanied by general symptoms shared with other types of cancer.

According to the statistics provided by the American Cancer Society, in 2019, approximately, 27,510 cases of stomach cancer will be diagnosed (17,230 in men and 10,280 in women) and 11,140 people will die from gastric cancer (6,800 men and 4,340 women).

Overall, the 5-year survival rate for people with gastric cancer is 31%. Cancer diagnosed at the localized stage have a 5 years survival rate of 67%.

Out of many risk factors associated with the onset of cancer, aging may be one of the major risk factors that cause the disease onset as cancer has been found to have a peak incidence between 50 and 70 years of age.

Dr. Saif MW said, "(In) a cross-sectional study was carried out on 1341 individuals (GC = 578, healthy = 763), who were stratified into two age groups: 35-59 years (middle-aged, n = 830) and ≥ 60 years (60 years-plus, n = 511)",...Age was clearly identified as a modifying factor on the risk projection of the combined states of Hp serology and sPG levels in gastric cancer screening, reflected by the augmented (~10.5 fold) risk of GC in the triple positive (Hppositive/sPGIlow/sPGI/IIlow) 60 year-plus subjects, which was not evident in the middle-aged group".

In the seeking a bioactive ingredient for the treatment of gastric cancer, researchers analyzed the role of 3,3'-diindolylmethane (DIM) on Forkhead box M1 (FOXM1) which is overexpressed in gastric cancer.

Used combined with paclitaxel, DIM significantly and dose-dependently inhibited the proliferation of SNU638 cells, compared to treatment with DIM or paclitaxel alone.

Furthermore, the combination also attenuated significantly the colony formation of SNU638 cells.

The combined treatment substantially increased apoptosis, indicated by increasing the level of proteins associated with the pro-apoptotic function.

Moreover, DIM dose-dependently sensitized gastric cancer cells by inhibiting the FOXM1 and potentiating the effects of paclitaxel.

Additionally, DIM significantly and dose-dependently inhibited protein kinase which plays a critical role in inducing proliferation in multiple cellular processes.

Dr. Jin H, the lead scientist said, "our results indicate that DIM effectively potentiates the efficacy of chemotherapeutic agents such as paclitaxel by downregulation of the Akt/FOXM1 signaling cascade in gastric cancer cells".

In order to reveal more information about DIM anti-gastric caner property, researchers gains investigated the cytotoxic effects of DIM in human gastric cancer cells. 

In human gastric cancer cell lines (SNU-1 and SNU-484), DIM significantly inhibited the proliferation in a dose-dependent manner.

DIM reduced the levels of proteins associated with cancer cell division and proliferation by increasing the expression of a gene associated with cancer suppression.

Interestingly, injection of DIM also increased the expression of enzymes in the induction of cell apoptosis while decreasing the expression of the anti-apoptotic protein.

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

Intake of 3,3'-diindolylmethane in the 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 potentiates paclitaxel-induced antitumor effects on gastric cancer cells through the Akt/FOXM1 signaling cascade by Jin H1, Park MH2, Kim SM. (PubMed)
(2) 3,3'-Diindolylmethane suppresses the growth of gastric cancer cells via activation of the Hippo signaling pathway by Li XJ1, Park ES, Park MH, Kim SM. (PubMed)
(3) Age-Specific Gastric Cancer Risk Indicated by the Combination of Helicobacter pylori Sero-Status and Serum Pepsinogen Levels by Sana Eybpoosh,1,2 Yeganeh Talebkhan,1 Samaneh Saberi,1 Maryam Esmaeili,1Akbar Oghalaie,1 Fatemeh Ebrahimzadeh,1 Toktam Karimi,1 Afshin Abdirad,3 Azin Nahvijou,4Mohammad Ali Mohagheghi,4 Mahmoud Eshagh Hosseini,5 and Marjan Mohammadi. (PMC)