Saturday, 20 April 2019

Phytochemical 3,3'-Diindolylmethane Kills Bladder Cancer Cells

By Kyle J. Norton

Scientists may have found a bioactive ingredient for the treatment of bladder cancer with no side effects, according to studies.

Bladder cancer is a medical and chronic condition characterized by irregular cell growth in the bladder tissues.

Most cases of bladder cancer begin in the cells on the surface of the inner lining of the bladder tissue before penetrating into the deeper layers of the bladder.

There are three types of bladder cancer classified depending on their origination.
* Transitional cell carcinoma
Transitional cell carcinoma starts in the innermost tissue layer of the bladder which can change shape and stretch without breaking apart. In other words,  they are able to stretch when the bladder is full and shrink when it is emptied.

More than 90 percent of bladder cancers begin in the transitional cells

* Squamous cell carcinoma
Cancer begins in squamous cells found in the tissues of the surface of the bladder, caused by long-term infection or irritation. 

About 8 percent of people with bladder cancers begin squamous cells.

* Adenocarcinoma
The cancer is originated from the glandular tissue of the bladder, including the surface layer of skin, glands and a variety of other tissue, due to long-term irritation and inflammation. 

Only 2 percent of people with the condition have a third bladder cancer type.

Regardless of the types of cancer originated, bladder cancer shares the general symptoms of other types of cancer accompanied by specific symptoms such as bladder spasms, blood in urine, frequent urination, pain or burning sensation during urination, pain in lower back and/or abdomen, inability to urinate, urinary urgency, reduced bladder capacity, and difficulty in urination. 

If you have some of the aforementioned symptoms, please make sure that you talk to your doctor to rule out the possibility of b bladder cancer.

Out of many risk factors associated with the onset of the diseases, smoking has been associated with most of the patients.

Dr. Neal D Freedman, wrote, "...the population attributable risk of bladder cancer for tobacco smoking is 50–65% in men and 20–30% in women and that current cigarette smoking triples bladder cancer risk relative to never smoking".

And, "Over the last 30 years, incidence rates have remained stable in the United States (men: 123.8/100,000 person-years to 142.2/100,000 person-years; women: 32.5/100,000 person-years to 33.2/100,000 person-years), yet changing smoking prevalence and cigarette composition warrant revisiting risk estimates for smoking and bladder cancer in more recent data".

In other words, if you are smokers, your risk of bladder cancer is substantially higher compared to never smoking individuals.

On finding a natural ingredient for the treatment of bladder cancer, researchers investigated the antiproliferative and anti-inflammatory potential effects of diindolylmethane (DIM) and lupeol on the experimental bladder cancer.

The study included 60 healthy male Wistar rats were selected and randomly divided into six groups, with 10 rats in each group.
* Group I: control.

* Group II: N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN; 150 mg/gavage/twice a week) for 8 weeks, and then they were given 100 ppm concentrations of dimethyl arsenic acid (DMA) in the drinking water for 28 weeks.

* Group III: BBN + DMA + DIM (5 mg/kg body weight (b.w.)/day) treatment was started after BBN treatment, and it was orally administered for 28 weeks)

* Group IV: BBN + DMA + lupeol (50 mg/kg b.w./day) treatment was started after BBN treatment, and it was orally administered for 28 weeks); and

* Groups V and VI: DIM and lupeol treatment alone for 36 weeks

At the final day of the experiment, DIM and lupeol treatment showed the inhibition of tumor growth in the bladder by histopathological confirmations and increased the expression of a protein associated with tumor suppression.

According to the Western blot analysis, the inhibition of bladder cancer also was accompanied by decreasing the production of proinflammatory cytokines.

Furthermore, DIM and lupeol treatment significantly decreased the levels of an enzyme associated with a mediator of tumor repopulation (Cox-2) in bladder tissue samples and NMP 22 in urine samples.

Moreover, in order to reveal more information of DIM anti-bladder cancer property, researchers to investigate the apoptotic properties of Diindolylmethane (DIM) and Lupeol on N-Butyl-N-(4-hydroxybutyl) Nitrosamine (BBN) initiated and Dimethylarsinic Acid (DMA) in the promotion of urinary bladder cancer.

The experiment included 60 male Wistar rats divided into 6 groups. Group I: Control. Group II: Rats were experimentally developed bladder carcinogenesis with BBN and DMA. Group III and IV: DIM and lupeol were administered after BBN treatment for 28 weeks. Group V and VI: DIM and lupeol alone treatment for 36 weeks.

During the study, DIM and lupeol induced cancer cell apoptosis and inhibited cell proliferation by activated the stimulation of proteins associated with cell death programming and deactivated the gene associated with cell differentiation and division.

In other words, administration of DIM and lupeol inhibited the progression of bladder cancer, by promoting the expression of apoptotic Bax, caspase-3, caspase-9 and inhibiting the expression of anti-apoptotic Bcl-2, PCNA in the urinary bladder of rats.

Dr. Prabhu B, the lead scientist wrote in the final report, "Administration of diindolylmethane and lupeol treatment induces apoptosis and cellular proliferation by its anti-carcinogenic properties. From our results, DIM and lupeol would be the agent or adjunct for the treatment of bladder carcinogenesis".

Taken altogether, 3,3'-Diindolylmethane may be considered a supplement for the prevention and treatment of bladder 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) Antiproliferative and anti-inflammatory properties of diindolylmethane and lupeol against N-butyl-N-(4-hydroxybutyl) nitrosamine induced bladder carcinogenesis in experimental rats by Prabhu B1, Balakrishnan D1, Sundaresan S. (PubMed)
(2) Diindolylmethane and Lupeol Modulates Apoptosis and Cell Proliferation in N-Butyl-N-(4-Hydroxybutyl) Nitrosamine Initiated and Dimethylarsinic Acid Promoted rat Bladder Carcinogenesis by Prabhu B1, Sivakumar A1, Sundaresan S. (PubMed)
(3) Association between smoking and risk of bladder cancer among men and women by Neal D Freedman, PhD, MPH,1 Debra T Silverman, ScD, ScM,1 Albert R Hollenbeck, PhD,2Arthur Schatzkin, MD, DrPH,1 and Christian C Abnet, PhD, MPH. (PMC)

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