PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancer

Prostate cancer (PCa) is a common malignant tumor, whose morbidity and mortality keep the top three in the male-related tumors in developed countries. Abnormal ion channels, such as transient receptor potential canonical 6 (TRPC6), are reported to be involved in the carcinogenesis and progress of prostate cancer and have become potential drug targets against prostate cancer. Here, we report a novel small molecule inhibitor of TRPC6, designated as PCC0208057, which can suppress the proliferation and migration of prostate cancer cells in vitro , and inhibit the formation of Human umbilical vein endothelial cells cell lumen. PCC0208057 can effectively inhibit the growth of xenograft tumor in vivo . Molecular mechanism studies revealed that PCC0208057 could directly bind and inhibit the activity of TRPC6, which then induces the prostate cancer cells arrested in G 2 /M phase via enhancing the phosphorylation of Nuclear Factor of Activated T Cells (NFAT) and Cdc2. Taken together, our study describes for the first time that PCC0208057, a novel TRPC6 inhibitor, might be a promising lead compound for treatment of prostate cancer.