G_i2 Protein Inhibition Blocks Chemotherapy- and Anti-Androgen-Induced Prostate Cancer Cell Migration

We have previously shown that heterotrimeric G-protein subunit alphai2 (G alpha(i)2) is essential for cell migration and invasion in prostate, ovarian and breast cancer cells, and novel small molecule inhibitors targeting G alpha(i)2 block its effects on migratory and invasive behavior. In this study, we have identified potent, metabolically stable, second generation G alpha(i)2 inhibitors which inhibit cell migration in prostate cancer cells. Recent studies have shown that chemotherapy can induce the cancer cells to migrate to distant sites to form metastases. In the present study, we determined the effects of taxanes (docetaxel), anti-androgens (enzalutamide and bicalutamide) and histone deacetylase (HDAC) inhibitors (SAHA and SBI-I-19) on cell migration in prostate cancer cells. All treatments induced cell migration, and simultaneous treatments with new G alpha(i)2 inhibitors blocked their effects on cell migration. We concluded that a combination treatment of G alpha(i)2 inhibitors and chemotherapy could blunt the capability of cancer cells to migrate and form metastases.