Diindolylmethane (DIM): Can This Compound Help fight Cancer?

Diindolylmethane (DIM) is a natural substance found in vegetables like broccoli, cabbage, and cauliflower. Sold as a supplement this compound is thought to provide various health benefits and is currently studied for its potent anti-cancer properties!

Introduction: What is it?

Diindolylmethane (DIM) is the main metabolite of indole-3-carbinol (I3C) which is a substance with strong anti-cancer, anti-inflammatory, and chemopreventive properties (R).

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Epidemiologic evidence suggests that high dietary intake of Brassica vegetables such as broccoli, cabbage and Brussels sprouts, protects against tumorigenesis in multiple organs. 3,3-Diindolylmethane is one of the promising anti-tumor agent derived from Brassica vegetables (R).

The National Cancer Institute of the United States has begun clinical trials of Diindolylmethane as a therapeutic for numerous forms of cancer (R1, R2).

Currently, Diindolylmethane is used to treat Recurrent Respiratory Papillomatosis (RRP) and as a traditional adjuvant medical therapy for pediatric recurrent respiratory papillomatosis (R).

Health Benefits of Diindolylmethane

1) Diindolylmethane Helps Prevent Cancer

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In a Double-blind randomized placebo-controlled multicenter clinical trial study, the use of DIM in the form of intravaginal suppositories proved its effectiveness in patients with Cervical Intraepithelial Neoplasia (CIN) I–II. The Study showed that this approach could be a better option for young women with CIN I-II (R).

Diindolylmethane promotes the production of prostate apoptosis response-4 (PAR-4) which is a specific protein within the body that selectively kills prostate cancer cells. It can also diminish cancer cell activity and restrict cell growth (R).

DIM inhibits prostate cancer development in the transgenic adenocarcinoma mouse prostate model (inhibits prostate carcinogenesis via induction of apoptosis and inhibition of cell cycle progression) (R).

Diindolylmethane within cruciferous vegetables can suppress gastric cells by triggering the Hippo signaling pathway and prevent the growth of gastric cancer cells (R, R2).

Diindolylmethane suppresses the growth of the human esophageal squamous cancer cells by arresting the G1 cell cycle (R).

DIM has many ways in which it affects breast cancer in the body. It has the power to prohibit the growth of breast cell cancer by modulating the aryl hydrocarbon receptors and reducing oxidative stress (R). DIM also caused cell death in specific breast cancer cells in culture dishes.

Diindolylmethane has the power to reduce the spread of breast tumors by stopping cell growth and movement of breast cancer cells (R).

Diindolylmethane derivatives used with ultra-flexible nanocarriers increases permeability across the skin and skin deposition. It also delays the formation of ultraviolet-induced tumors in the skin and can reduce the numbers of tumors that are prevalent (R).

Treatment with diindolylmethane prevents cell production and prompts cell death in cervical cancer cells, HeLa (adenocarcinoma cells) and SiHa (squamous carcinoma cells). HeLa cells were affected the most in treatment. Diindolylmethane also increased the radiosensitivity of HeLa cells (R).

Studies conducted in various populations suggest that the consumption of vegetables containing 3,3-diindolylmethane (DIM) such as cabbage , broccoli and brussels sprouts decreases the risk of developing liver cancer (R1, R2).

DIM is also a promising naturally occurring anti-estrogen which can be used as a therapeutic regimen to treat thyroid cancer (R).

DIM only kills cancer cells without toxicity to normal cells (R).

2) Diindolylmethane Regulates Estrogen

Diindolylmethane enhances estrogen metabolism in Thyroid Proliferative Disease (TPD) patients and can potentially serve as an antiestrogenic dietary supplement to help reduce the risk of developing Thyroid proliferative disease (RR2).

In a pilot study, DIM increased the 2-hydroxylation of estrogen urinary metabolites in postmenopausal women with a history of early-stage breast cancer. It has been shown that DIM could protect against hormone-dependent cancers (R).

DIM synergistically acts with genistein to decrease the adverse effects of estrogen in LNCaP and PC-3 prostate cancer cells (R).

DIM reduces the production of certain estrogen metabolites that have the ability to cause cancer (carcinogenic) and breast tumor development (R).

3) Diindolylmethane Protects The Liver

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DIM exerts an anti-fibrosis, anti-tumor, antioxidant, immunomodulatory, detoxification and anti-inflammation effects on liver protection. It also reduces microbial-induced liver injuries (R).

DIM ameliorates experimental liver fibrosis induced by thioacetamide in mice (R).

In one study DIM blocked Hepatocellular Carcinoma (HCC) cell metastasis by suppressing tumor cell migration and invasion in mice (R).

DIM reduces steatosis and the progression of Nonalcoholic Steatohepatitis (NASH) in methionine-cholinediet-induced NASH in mice. This was by the induction of Treg dominance to reduce intrahepatic inflammation (R).

Diindolylmethane could effectively suppress acute liver inflammation caused by Staphylococcal Enterotoxin B (SEB) and thus reduced SEB-mediated liver injury in mice (R).

4) Diindolylmethane Helps Reduce Hematopoietic Injury Caused by Radiation

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DIM mitigates Total Body Irradiation (TBI) induced hematopoietic injury in mice. Therefore it has the potential to be used as an effective radioprotectant to prevent TBI-induced hematopoietic injury (R).

5) Diindolylmethane Suppresses Vascular Smooth Muscle cell Phenotypic Modulation

DIM could suppress the phenotypic modulation of Vascular Smooth Muscle Cells (VSMCs) and neointima hyperplasia after vascular injury in mouse carotid arterial injury model. Infiltration of inflammatory cells was also inhibited by DIM administration (R).

6) Diindolylmethane May Help Control Obesity

In one study Indole-3-carbinol (5 mg injections) treatment decreased body weight fat accumulation and infiltrated macrophages in the adipose tissue of high-fat-diet-induced obese mice (R).

7) Diindolylmethane Helps Control Infections

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Diindolylmethane is considered the most common drug in adjuvant therapy for Recurrent Respiratory Papillomatosis (RRP) and could be considered for patients for whom surgical management fails to control their disease (R1, R2).

In a prospective open-label study design in patients with Recurrent respiratory papillomatosis, treatment with indole-3-carbinol caused 33% of the patients experience a remission of papillomatous growth and did not require surgery while 30% of the patients had a reduction in papillomatous growth (R).

A case report available suggests that an 8-year-old girl reported a disappearance of Recurrent respiratory papillomatosis over a 27 month period with the use of intralesional and intravenous Cidofovir in association with indol-3-carbinol (R).

Key Molecular Targets of Diindolylmethane

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Technical

  • 40 μM DIM for 48h induces ESCC apoptosis, G1-phase cell cycle arrest, reduces levels of Cyclin D1 and Cyclin E2, and CDK4 and CDK6
  • DIM can bind to aryl hydrocarbon receptors which promote the transcription of genes that stimulate the phase I cytochrome P450 (CYP) family
  • Exposure to DIM reduces the expression of both vascular endothelial growth factor and metalloproteinase-9 via downregulation of transcription factor Forkhead box M1 (FoxM1)
  • B-DIM, at low doses (20 μmol/L) induces Par-4, in L3.6pl and Colo-357 pancreatic cancer cells.
  • By stimulating the Hippo signaling pathways, DIM improves cell fate determination, cell growth and death, cell division, and reduces tumor production in gastric cancer.
  • diindolylmethane stops esophageal cancer cell growth (proliferation) by causing cell death (apoptosis) and G1-phase cell cycle arrest (R).
  • It can act as an anti-initiating agent that prevents the mutation of DNA, which is the first stage in cancer development. DIM has the ability to trigger cell detox and reduce inflammation that could also cause cancer.
  • The anti-cancer properties of DIM consist of the reduction in the development of new capillaries (angiogenesis), the initiation of controlled cell death, and the prevention of cell growth (R).
  • DIM also increases anti-inflammatory properties of hormone-responsive cell lines by activating certain estrogen receptor βtarget genes

Dosage

Diindolylmethane is well tolerated at single doses of up to 200 mg according to a Randomized study conducted in healthy subjects (R).

Also, oral DIM at 2mg/kg/day is well tolerated with no significant toxicity according to another randomized controlled pilot study (R).

Side Effects

According to one study, DIM had side effects on some sperm characteristics led to the histological degeneration of testicular tissues in male rats (R).

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