Friday, June 29, 2012

Rhosin - New Drug For Stopping Growth Of Cancer Cells

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Main Category: Breast Cancer
Also Included In: Cancer / Oncology
Article Date: 28 Jun 2012 - 9:00 PDT

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A new candidate drug developed by researchers at Cincinnati Children's Hospital Medical Center has shown to stop breast cancer cells from metastasizing, according to a report published online in Chemistry & Biology.

In addition, the drug named Rhosin was also found to promote growth of early nerve cells called neurites. The new drug may hold promise for the treatment of various cancers or nervous system damage.

Rhosin precisely targets a single component of a cell signaling protein complex called Rho GTPases. Rho GTPases controls cell growth and movement throughout the body.

Yi Zheng, Ph.D., lead researcher and director of Experimental Hematology and Cancer Biology at Cincinnati Children's, explained:

"Although still years from clinical development, in principle Rhosin could be useful in therapy for many kinds of cancer or possible neuron and spinal cord regeneration. We've performed in silica (computerized) rational drug design, pharmacological characterization and cell tests in the laboratory, and we are now starting to work with mouse models."

For several years researchers have tried to identify safe and effective therapeutic targets for specific parts of Rhp GTPases, particularly for RhoA. RhoA is the center protein in Rho GTPases and is vital for the signaling function of the complex.

For example, enhanced RhoA activity in breast cancer makes the cancerous cells more invasive and causes them to metastasize. However, a deficiency of RhoA prevents cancer growth and progression.

Zheng explains that even with this knowledge researchers have been unable to successfully develop an effective small-molecule inhibitor for RhoA.

In this study, the team examined research describing the processes and functions of Rho GTPases and then used computerized molecular screening and computerized drug design in order to identify a druggable target site.

This technology also provided the researchers with a preliminary virtual simulation on the potential effectiveness of candidate drugs.

According to Zheng, the globular structure of RhoA makes it difficult for a small-molecule inhibitor to attach. However, the team found that Rhosin was able to effectively bind to two shallow surface grooves on the protein. As a result the drug was able to begin affecting cells.

The team also set out to determine whether the drug was effective at blocking guanine nucleotide exchange factors (GEFs). Guanine nucleotide is a vital energy source and signaling component of cells. GEFs need to be activated in order to set off the regulatory signaling of GTPases.

Once laboratory cells tests confirmed that Rhosin was able to target and bind to RhoA, the team then tested the drug's effect on cultured breast cancer cells and nerve cells.

According to the researchers, the drug was able to prevent cell growth in breast cancer cells without disrupting other vital cellular processes or affecting non-cancerous breast cells. These findings suggested that the drug is effective in targeting RhoA-mediated breast cancer proliferation.

In addition, the team treated neuronal cells with the drug, along with nerve growth factor, a protein that is vital to the growth and survival of neurons. Rhosin worked with nerve growth factor in a dose-dependent way to promote the proliferation of branching neurites from the neuronal cells.

Written by Grace Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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Grace Rattue. "Rhosin - New Drug For Stopping Growth Of Cancer Cells." Medical News Today. MediLexicon, Intl., 28 Jun. 2012. Web.
28 Jun. 2012. <http://www.medicalnewstoday.com/articles/247218.php>


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'Rhosin - New Drug For Stopping Growth Of Cancer Cells'

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Source: http://www.medicalnewstoday.com/articles/247218.php

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