Tuesday, 6 November 2018

The Plant Base Bioactive Indole-3-Carbinol, in the Prevention and Treatment of Lung Cancer

By Kyle J. Norton

Indole-3-carbinol, an organic compound found in cruciferous vegetables may process a potential in reducing risk and treatment of lung cancer, some scientists found.

Lung cancer is a class of chronic and medical disease caused by irregular cells growth originated from the inner lining of the lung tissue due to the DNA alternation.

At the advanced stage after colonizing most parts of the lung, the cancerous cells can travel from the primary site to infect other healthy tissue and organs a distance away.

 In the US, lung cancer is the leading cause of cancer deaths, causing 158,683 deaths, including 88,329 men and 70,354 women, according to the 2007 statistic.

Researchers do not the exact causes of lung cancer. As of today, no one knows why people with similar health conditions, family history, and race, some are susceptible to the early onset of the disease while others do not.

Some researchers suggested genetic mutation and long-term cigarette smoking are 2 major risk factors associated with the alternative of lung cell DNA.

Truly, according to the statistic, approximately 8% of lung cancers are inherited or occur as a result of a genetic predisposition.

Dr. Ahmed El-Telbany, the lead scientist in the study "Cancer Genes in Lung Cancer. Racial Disparities: Are There Any?" said, "Mutational analysis and genomics profiling in recent years have advanced the field of lung cancer genetics/genomics significantly. It is becoming more accepted now that the identification of genomic alterations in lung cancer can impact therapeutics, especially when the alterations represent “oncogenic drivers” in the processes of tumorigenesis and progression" and

 "The genes which are associated with lung cancer risk include EGFR, KRAS, MET, LKB1, BRAF, PIK3CA, ALK, RET, and ROS1".

Genetic mutation inherited from the parents is a result of an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing lung cancer.

However, not all people who carry the mutated lung cancer genes will develop lung cancer.

On the cigarette smoking in risk of lung cancer, researchers believe cigarette containing high amount of cancer-causing substances (carcinogens), when inhaled, the cigarette smoke carried the chemical toxins to the lung cell directly, and prolonged periods exposed to such chemicals can alternate lung cell DNA, leading to the early onset of lung cancer.

The joint study to examine the impact of smoking on risks of the major cell types of lung cancer led by the Institute of Ruhr Universität Bochum (IPA) included 13,169 cases and 16,010 controls from Europe and Canada suggested 
* Squamous cell carcinoma (SqCC) predominated in male smokers. 

* The ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for Adenocarcinoma (AdCa)

* Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% CI 74.8-143.2) for SqCC, 111.3 (95% CI 69.8-177.5) for small cell lung cancer (SCLC), and 21.9 (95% CI 16.6-29.0) for AdCa.

These result surely reconfirmed the epidemiological studies suggestion, long-term use of cigarettes is associated substantially increased the risk of lung cancer regardless of gender.

Indole-3-carbinol is a phytochemical in the class of Indoles found abundantly in cabbage, kale, Brussels sprouts, rutabaga, mustard greens, broccoli, etc.

With an aim to find the natural ingredient for the treatment of lung cancer without inducing any adverse effects, the University of Minnesota conducted a study to test the chemopreventive efficacy of indole-3-carbinol (I3C), a phytochemical found in cruciferous vegetables, to inhibit tobacco carcinogen-induced lung adenocarcinoma in A/J mice.

Before the infection of indole-3-carbinol (I3C), the tested mice were given a post-initiation or progression protocol.

Post-initiation administration of I3C decreased the multiplicity of surface tumors as well as all forms of histopathological lesions, including adenocarcinoma.

Further analysis the effect of  indole-3-carbinol (I3C), in  A549 lung adenocarcinoma cell line, researchers indicated that the lung cancer preventive effects of I3C are mediated, at least in part, via modulation of the receptor tyrosine kinase/PI3K/Akt signaling pathway in the inhibition of cell growth and proliferation.

However, administration of the compound during tumor progression failed to decrease the multiplicity of surface tumors and early forms of microscopic lesions but reduced the frequency of adenocarcinoma.

In vivo, administration of a mixture of low concentrations of I3C (50 μM) plus silibinin (50 μM) for 72 h also displayed a significant inhibition of cell growth through the expression of the extracellular signal-regulated kinase (ERK) and Akt activation in the induction of apoptosis of A549 and H460 lung cancer cells.

Moreover, in the examine, the effects of indole-3-carbinol (I3C), in a mixture of NNK plus BaP (2 micromols each), administered by gavage as eight biweekly doses caused 21.1 +/- 5.2 lung tumors in a mouse model.

* Lung cancer induced mice given diets containing I3C at 1, 10, 30, 71, and 112 micromol/g, beginning at 50% in the carcinogen treatment phase, had 17.9 +/- 6.1, 10.4 +/- 3.7, 9.8 +/- 5.1, 5.2 +/- 4.0, and 2.5 +/- 2.4 lung tumors per mouse, corresponding to reductions by 15%, 51%, 53%, 75%, and 88%, respectively.

* I3C was significantly effective at the lowest dose level (1 micromol I3C/g diet).

* Administration of I3C (112 micromols/g diet) beginning 1 week after the last dose of the carcinogen significantly reduced lung cancer induced by NNK plus BaP by 74%.

* I3C inhibited the lung cancer progression partly through the antiproliferative and apoptotic activity.

Dr. Kassie F, the lead scientist, at the final phase of the experiment said, "the efficacy of I3C in the prevention of tobacco carcinogen-induced lung tumorigenesis in A/J mice and provide a basis for future evaluation of this compound in clinical trials as a chemopreventive agent for current and former smokers".

 Taken altogether, phytochemical Indole-3-carbinol may be considered a functional bioactive compound for the prevention of lung cancer and a secondary therapy combined with the primary medicine for the treatment of lung cancer, depending to the further data collection of the large sample size and multi-center 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 used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.

(1) Indole-3-carbinol inhibited tobacco smoke carcinogen-induced lung adenocarcinoma in A/J mice when administered during the post-initiation or progression phase of lung tumorigenesis by Qian X1, Melkamu T, Upadhyaya P, Kassie F.(PubMed)
(2) Dose-dependent inhibition of tobacco smoke carcinogen-induced lung tumorigenesis in A/J mice by indole-3-carbinol by Kassie F1, Matise I, Negia M, Upadhyaya P, Hecht SS.(PubMed)
(3) Enhanced inhibition of lung adenocarcinoma by combinatorial treatment with indole-3-carbinol and silibinin in A/J mice by Dagne A1, Melkamu T, Schutten MM, Qian X, Upadhyaya P, Luo X, Kassie F.(PubMed)
(4) Cancer Genes in Lung Cancer Racial Disparities: Are There Any? by Ahmed El-Telbany1,2 and Patrick C. Ma. (PMC)

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