Monday, 25 March 2019

Plant-Based Bioactive Compound 3,3'-Diindolylmethane Kills Lung Cancer Cells in Vivo

By Kyle J. Norton

Lung cancer is a medical and chronic condition associated with the alternation of the cells in the lung tissue.

Most cases of lung cancer start in the cell on the surface of the inner lining of lung tissue before striking into deeper layers.

At the early stage, due to the small size of the tumor, most patients are asymptomatic. However, at the advanced stage, besides the common symptoms shared with other types of cancer, the patients may also experience symptoms of difficult breathing, persistent cough and hoarseness, and chest pain.

Some patients may also vomit blood caused by the oversize tumor suppressing on the nearby blood vessels.

Lung cancer is diagnosed mostly in the elderly, particularly in people over 65 years of age.
The mortality rate of lung cancer is higher than the colon, breast, and prostate cancers combined.

According to the statistics, In Canada, the 5-year net survival for lung cancer is 17%.

In other words, on average, only 17% of people diagnosed with lung cancer will survive for at least 5 years after their diagnosis.

However, lung cancer at the early localized stage has 5 years of the survival rate of 60%.

Although there are many risk factors associated with the onset of lung cancer, smoking is considered epidemiologically a major cause of the disease onset.

Dr. Ozlü T, the lead scientist in the examination of smoking and lung cancer risk, "The association between cigarettes and lung cancer has been proven by large cohort studies. Tobacco use has been reported to be the main cause of 90% of male and 79% of female lung cancers. 90% of deaths from lung cancer are estimated to be due to smoking. The risk of lung cancer development is 20-40 times higher in lifelong smokers compared to non-smokers".

And, "After smoking cessation, the cumulative death risk from lung cancer decreases. Patients who continue smoking experience greater difficulties during cancer treatment. Stopping smoking may prolong survival in cancer patients, and also decreases the risk of recurrent pulmonary carcinoma".

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 in the concern about the risk of inflammatory conditions of the lung such as chronic obstructive pulmonary disease (COPD) that contributes to the onset of lung cancer risk, particularly lung squamous cell carcinoma (LSCC) examined the chemopreventive effects of BioResponse diindolylmethane (DIM).

The study included a mouse model of inflammation-driven LSCC induced by N-nitroso-trischloroethylurea (NTCU) and enhanced by lipopolysaccharide (LPS), a potent pro-inflammatory agent contained in tobacco and tobacco smoke.

Before treatment of DIM, mice treated with the combination of NTCU and LPS had a 9-fold increase in the number of bronchioles with LSC.

Compared to mice treated with LPS alone, mice treated with NTCU plus LPS showed significantly increased expression of the pro-inflammatory cytokines, accompanied by the increased expression of proteins associated with the production of pro-inflammation and cancer cells initiation.

Pretreatment of DIM at a concentration of 0 μmol/g diet or 2,460 ppm) to mice treated with NTCU plus LPS reduced the incidence of LSCC by 2-fold and suppressed activation/expression of proinflammatory and procarcinogenic proteins without affecting the expression of cytokines and p53, a tumor suppressive gene.

In other words, DIM blocked the development of LSCC through cytotoxicity and gene associated with tumor suppression.

In order to reveal more information about DIM anti-lung cancer property, researchers looked into the anticancer efficacy of 1,1-bis (3'-indolyl)-1-(p-biphenyl) methane (DIM-C-pPhC₆H₅) inhalation delivery alone and in combination with i.v. docetaxel in a murine model.

According to assays, the lung weight reduction in mice treated with the drug combination was 64% compared with 40% and 47% in mice treated with DIM-C-pPhC₆H₅ aerosol and docetaxel alone, respectively.

The combination treatment inhibited the lung cancer by decreased expression of proteins associated with the pro-inflammatory cytokines, cancer cells survival, and proliferation through stimulating the production of the new blood vessels.

Furthermore, the combination also increased expression of genes involved autophagy in the tumor formation, compared to the tumor cell counts from single-agent treatment and control groups.

Dr. Ichite N, the lead scientist said, "These results suggest that DIM-C-pPhC₆H₅ aerosol enhanced the anticancer activity of docetaxel in a lung cancer model by activating multiple signaling pathways".

Taken altogether, 3,3'-Diindolylmethane may be considered a supplement for the prevention and combined with primary medicine for the treatment of lung 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 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.

(1) Dietary diindolylmethane suppresses inflammation-driven lung squamous cell carcinoma in mice by Song JM1, Qian X1, Teferi F1, Pan J2, Wang Y2, Kassie F. (PubMed)
(2) Inhalation delivery of a novel diindolylmethane derivative for the treatment of lung cancer by Ichite N1, Chougule M, Patel AR, Jackson T, Safe S, Singh M. (PubMed)
(3) Smoking and lung cancer by Ozlü T1, Bülbül Y. (PubMed)

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