Wednesday, 7 June 2023

#Phytochemical 3,3'-Diindolylmethane Inhibits #ColorectalCancer Through Some Unknown Mechanisms, Researchers Find

By Kyle J. Norton

3,3'-Diindolylmethane or DIM may be used as a bioactive compound for the treatment of colorectal cancer with no side effects, according to studies.

Colorectal cancer is a medical condition caused by cell growth irregularly in the tissue of the colon or rectum due to the alternation of cells' DNA.

According to the statistics provided by the American Cancer Society, in the US, colorectal cancer is the third most common cancer diagnosed in both men and women compared to other types of cancer.

The lifetime risk of colorectal cancer is 1 in 22 (4.49%) for men and 1 in 24 (4.15%) for women.

Approximately, 140,000 cases of colorectal cancer were diagnosed in the US in 2018. Cancer also causes the death of over 50, 000 people, representing 8.3% of total cancer death.

Being overweight or obese. smoking, physical inactivity, excessive alcohol drinking, increased in age, family and personal history, and genetic preposition are some of the prevalent risks of the disease.

Some researchers suggested that an unhealthy diet such as the promotion of the Western diet over the past few decades may be one of the major causes of colorectal cancer.

Dr. Alan Moss, the lead scientist in the evaluation of the association between diet and colorectal cancer risk, wrote, "Studies that examined dietary factors and various cancers showed that one of the strongest associations is between CRC and meat consumption"

And "Recently, global publicity was generated by the World Health Organization International Agency for Research on Cancer consensus statement regarding the increased risk of CRC with consumption of processed or red meat.4 The 2015 statement notes that processed meat is carcinogenic to humans and lists processed meat as a group 1 substance. Processed meats result from salting, smoking, fermenting, or curing the meat, and common examples include ham, bacon, and sausage".

The results clearly suggested that by changing your diet pattern from the Western diet to a traditional diet with high fruits and vegetables, your risk of colorectal can be reduced substantially.


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, kale, etc.

Researchers concerned about the slow growth of colorectal cancer and the prognosis in colorectal cancer patients examined the effects of 3,3'-Diindolylmethane (DIM) on cyclin D1, which was aberrantly overexpressed in colorectal cancer cells and tumors.

Where cyclin D1 is a protein needed for cellular proliferation in the G1 phase of the cell cycle.

Injection of DIM inhibited the cyclin D1 expression in colorectal cancer cells (CRC), without affecting the PPARĪ³ expression and protease activity in regulating the process of cell differentiation.

Moreover, DIM inhibition of the cell cycle in the G1 phase of colorectal cancer cells (CRC) without alternating the cyclin D1 mRNA expression. The results suggested DIM modulated cyclin D1 expression at the translational level through some unknown mechanisms.

Dr. Zhang X and colleagues wrote in the final report, "The present study demonstrates that DIM downregulates cyclin D1 through triggering ER stress in human colorectal cancer cells".


In other words, DIM-induced cell cycle arrest of the colorectal cancer cells by modulating the G1 phase of the cell cycle.

Additionally, in order to reveal more information about the DIM anti-colorectal cancer activity, researchers elucidated the molecular mechanism of ATF3 induction by DIM in human CRC cells.

The DIM treatment induced apoptosis and induced ATF3 gene expression at protein and messenger RNA levels, involving the DNA repair of the damaged cells.

However, in colorectal cancer cells, deletion and point mutation of the ATF binding site (-23 to -16) abolished ATF3 promoter activation by DIM, leading to overexpression of ATF4 associated with the promotion of metabolic homeostasis and cancer cell survival

In other words, DIM stimulates ATF3 expression inducing apoptosis in human colorectal cells by inhibiting the ATF4-mediated pathway.

Taken altogether, 3,3'-Diindolylmethane derived from I3C may be considered a supplement for the prevention and combined with primary therapy for the treatment of colorectal cancer, pending the confirmation of large sample size and multicenter human study.

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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 referenced in medical research, such as the international journal Pharma and Bioscience, ISSN 0975-6299.

Sources
(1) 3,3'-diindolylmethane downregulates cyclin D1 through triggering endoplasmic reticulum stress in colorectal cancer cells by Zhang X1, Sukamporn P2, Zhang S3, Min KW4, Baek SJ. (PubMed)
(2) 3,3'-diindolylmethane induces activating transcription factor 3 (ATF3) via ATF4 in human colorectal cancer cells by Lee SH1, Min KW, Zhang X, Baek SJ. (PubMed)
(3) The Association Between Diet and Colorectal Cancer Risk: Moving Beyond Generalizations
Alan Moss, and Kumanan Nalankilli. (Gastroenterology)

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