Brusatol Suppresses Bladder Cancer by downregulating the expression of Nrf2

Abstract

Abstract A substance called brunsatol, which is derived from the dried ripe fruit of Brucea javanica, has been shown to be active against a variety of human cancers, but not against bladder cancer (BCa). In the present study, we attempted to investigate the effect of brusatol in BCa and verify whether Nrf2 was involved in the mechanism. The effect of brusatol was assessed by CCK8 and colony formation assays. Transwell analysis were performed to detect the migration of bladder cancer cell lines under treatment of brusatol. Apoptosis was determined by flow cytometry. Finally, Western blot was used to explore the mechanism of brusatol regulating the BCa progression and Nrf2. We revealed that brusatol inhibited the growth of BCa cells in vitro and in vivo and decreased their invasion ability. Mechanistic analysis revealed that brusatol decreased the expression of Nrf2 which functions as a tumor promoter in the development of BCa. And Nrf2 overexpression reversed the inhibitory effects induced by brusatol. Finally, brusatol inhibited the proliferation and invasion of BCa cells via Akt signaling-mediated Nrf2 expression. These results suggest that brustasol is a valuable potential antitumor drug available for BCa.