Prostate Cancer Cure: An Exciting Start

Small molecule may play a big role in cancer treatment

NanoNewsNet based on UT Dallas: Small Molecule Could Have Big Impact on Prostate CancerDr. Jung-Mo Ahn, associate professor of chemistry at The University of Texas at Dallas, has developed and synthesized a new low-molecular compound that can become a formidable weapon in the fight against prostate cancer.

According to the American Cancer Society, approximately 239 thousand residents of the country will be diagnosed with prostate cancer in 2013 and about 30 thousand will die from this disease.

In an article published online in the journal Nature Communications (Ravindranathan et al., Peptidomimetic targeting of critical androgen receptor-coregulator interactions in prostate cancer), Dr. Ahn and his colleagues from the Southwestern Medical Center (Southwestern Medical Center) UT describe the structure of this molecule (peptidomimetics D2), as well as laboratory tests confirming its effectiveness in blocking the function of androgen receptor proteins that contribute to the development of cancer.

Androgen receptors are located inside cells and have complex surfaces with many "docking blocks" in which various proteins interact with them. Each such motif has a unique structure, and a molecule capable of interacting with it must have an affinity for it.

Androgens, such as testosterone, are the main molecules that bind to androgen receptors. Such binding sets in motion a chain of events that activates several different processes in the human body, including the development and preservation of characteristic male sexual characteristics.

In search of a new approach to the treatment of prostate cancer, Dr. Ahn and his colleagues stopped at blocking one of the most important motives on androgen receptors.

"In the process of tumor growth, activation of this motif provides it with what it needs," explains Dr. Ahn. "There are other surfaces on the androgen receptor that can freely continue to function, working with their corresponding proteins. We tried to block only one of the types of interactions – the one that promotes the growth of prostate cancer. Therefore, we believe that our approach can be highly effective and have fewer side effects."

Using computer modeling, Dr. Ahn created a small spiral-shaped molecule that exactly corresponds to the pocket on the androgen receptor associated with the development of prostate cancer. In collaboration with Dr. Ganesh Raj, an associate professor of urology at TU and a specialist in the treatment of urological cancers, the researchers tested this compound on animals and isolated human tissues.

Showing no noticeable toxicity, it prevented the interaction of androgen receptors with their partner proteins and blocked the growth of tumor cells.

The figure from the article in Nature Communications shows the superimposition of the peptidomimetic D2 (green) on the crystal structure of the LXXLL motif.

"We have shown that our molecule, due to its high affinity, binds very tightly to the androgen receptor," says Ahn. "In addition, we have confirmed that it inhibits the function of androgens in these cells, which is a promising discovery for drug development. We have shown that it really works with these mechanisms and suppresses the proliferation of prostate cancer cells as effectively as other compounds currently undergoing clinical trials."

Dr. Ahn plans to continue his research to better understand how his small molecule and its close compounds work against cancer at the molecular level. There is still a lot of work to be done before the creation of a potential drug, but, according to him, "this is an exciting start."

Portal "Eternal youth" http://vechnayamolodost.ru04.06.2013