Posts Tagged ‘DIM’

Targeting bone turnover by nature-derived agents for deriving effective treatment of PCa metastases

Reporter: Ritu Saxena, Ph.D.

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Introduction and basis of research: Prostate Cancer (PCa) is a leading cause of cancer-related deaths in the men of United States. Metastasis development results in high mortality rate in prostate cancer patients and PCa frequently metastasizes to the bone.

Using nature-derived agents, scientists at the Wayne State University School of medicine, Detroit, Michigan targeted bone remodeling – both bone formation and bone resorption, and proposed it as an effective strategy for the treatment of PCa bone metastasis. The treatment strategy was based on the recent observations pointing towards an increase in both osteoclastic activity and osteoblastic activity in PCa bone metastases which is contrary to the earlier belief that metastases is osteoblastic. Thus, authors designed a study targeting that both osteoclasts (bone forming cells) and osteoclasts (bone resorbing cells) activity for the treatment of PCa bone metastases

Study design: Li et al utilized formulated isoflavone and 3,39-diindolylmethane (BR-DIM) for the suppression of bone remodeling in PCa bone metastases. 3,39-diindolylmethane (DIM) is a natural agent mainly found in the members of the family Cruciferae such as broccoli, and Isoflavone is mainly found in soyabean. Isoflavone genistein has been reported to have the ability to inhibit cancer cell growth both in vitro and in vivo without toxicity. BR-DIM (manufactured by BioResponse, LLC.), as stated by the authors “could downregulate the expression of AR, Akt and NF-kB, leading to the inhibition of PCa growth and the induction of apoptosis in vitro”.  Authors thus, set out to test the hypothesis that “ a mixture of isoflavone and BR-DIM could inhibit the differentiation of osteoclasts and osteoblasts mediated through regulation of cellular signaling pathways that are involved in bone remodeling and PCa bone in vivo”.

A co-culture system involving pre-osteoclastic cell line-RAW264.7 cells, pre-osteoblastic cell line hFOB1.19, and several PCa cell lines, was established to determine how the PCa cells affect differentiation of bone cells. The effect of isoflavone and BR-DIM was then tested on both osteoclast and osteoblast differentiation and PCa cells in the co-culture system.

Results: Isoflavone and BR-DIM inhibited bone remodeling through the inhibition of cell signal transduction associated with osteoclast differentiation (RANKL-mediated signaling), osteoblast differentiation (RUNX2, periostin gene), and PCa growth and signaling. Isoflavone and BR-DIM, infact, were shown to affect multiple signaling pathways that could possibly be useful in the prevention of PCa progression especially in the context of bone metastases.

The study highlights an important message that natural agents could be a source for deriving agents that could be useful in the treatment of diseases such as cancer without toxicity issues.

Sources: Research Article – Li Y, Kong D, Ahmad A, Bao B, Sarkar FH. Targeting bone remodeling by isoflavone and 3,3′-diindolylmethane in the context of prostate cancer bone metastasis. PLoS One. 2012;7(3):e33011. http://www.ncbi.nlm.nih.gov/pubmed?term=22412975

UroToday report: http://www.urotoday.com/UroToday/Prostate-Cancer/targeting-bone-remodeling-by-isoflavone-and-3-3-diindolylmethane-in-the-context-of-prostate-cancer-bone-metastasis-beyond-the-abstract-by-fazlul-h-sarkar-phd-et-al.html

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Reporter: Prabodh Kandala, PhD

You know that vegetables are good for you. And cruciferous vegetables – broccoli, cabbage, cauliflower, brusselsprouts – are especially healthful. New studies are demonstrating the anti-cancer effects of an ingredient in these green goddesses.

Diindolylmethane (DIM) is the wonder ingredient found in cruciferousvegetables. DIM is also sold over-the-counter as a supplement.

Researchers have found that DIM kills ovarian cancer cells in the laboratory and also improves the effectiveness of a commonly used chemotherapy agent.

Prabodh K. Kandala and Sanjay K. Srivastava, researchers in the Department of Biomedical Sciences and Cancer Biology Center at Texas Tech University Health Sciences Center, made the discoveries.

Researchers already knew that DIM slows the growth of ovarian cancer cells. In a detailed look at how the chemical behaves, they learned that DIM works by blocking the gene STAT3, which is seen in 90 percent of ovarian cancers.

In addition to causing cell death, DIM also prevented the cancer cells from invading or developing blood vessel structures which are key processes in cancer growth.

A platinum-based chemotherapy drug – cisplatin – is used to treat women with ovarian cancer. The drug doesn’t always work, though, and some patients become resistant to it.

For this study, researchers found that when DIM was combined withcisplatin, tumor growth in mice was slowed 50 percent more than when the chemo was used alone.

“DIM increases the effect of cisplatin, without being toxic to normal ovarian cells, by targeting STAT3 signaling and increasing apoptosis,” the authors explained.

“Cisplatin is very toxic and has severe side effects. If co-treatment with DIM means that a low dose of cisplatin can be given to patients without the loss of therapeutic effect, but with reduced side effects, it would represent a significant breakthrough in clinical practice,” Kandala andSrivastava concluded.

For the experiments, the supplement BioResponse DMI was used.

A number of clinical trials are currently under way to study the impact of DIM on a variety of malignancies including cancers of the breast, prostate, pancreas, kidney and others.

This new research was published in BioMed Central‘s open access journalBMC Medicine.




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