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Scientists use natural agents for prostate cancer bone metastasis treatment

Posted in Bone Disease and Musculoskeletal Disease, CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Signaling & Cell Circuits, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Uncategorized, tagged , , , , , , , , , , , , , on September 17, 2012| 9 Comments »

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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