Rhosin Blocks the Stimulating Activity of RhoA in Breast Cancer Cells

The candidate low molecular weight drug Rhosin was found to have pronounced effects on in vitro breast cancer cell cultures as well as on cultures of neuronal cells.

Rhosin was discovered by investigators at the Cincinnati Children's Hospital Medical Center (Ohio, USA) who coupled advanced high-throughput molecular screening with computerized drug design software to identify a druggable target site on the critical protein component of the Rho GTPase signaling complex, RhoA.

RhoA is essential for the signaling function of the Rho GTPase complex. Previous studies have shown that in breast cancer increased RhoA activity stimulated cancer cell invasiveness and spreading, while RhoA deficiency suppressed cancer growth and progression. In addition to its role in breast cancer, imbalance in Rho GTPas activity has been implicated in other human diseases, including various cancers and neurological disorders.

In the current study, which was published in the June 21, 2012, online edition of the journal Chemistry & Biology, the investigators treated breast cancer and neuronal cell cultures with Rhosin. They reported that Rhosin specifically inhibited RhoA activity and RhoA-mediated cellular function without affecting other signaling activities. By suppressing RhoA activity, Rhosin inhibited mammary sphere formation by breast cancer cells and inhibited invasion of mammary epithelial cells. In the neuronal cell cultures, Rhosin induced neurite outgrowth of PC12 cells in synergy with nerve growth factor (NGF).

"Although still years from clinical development, in principle Rhosin could be useful in therapy for many kinds of cancer or possibly neuron and spinal cord regeneration," said senior author Dr. Yi Zheng, professor of experimental hematology and cancer biology at Cincinnati Children's Hospital Medical Center. "We have performed in silica rational drug design, pharmacological characterization, and cell tests in the laboratory, and we are now starting to work with mouse models."

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Cincinnati Children's Hospital Medical Center