Brusatol hinders the advancement of bladder cancer by Chac1/Nrf2/SLC7A11 pathway

Abstract Background Bladder cancer, also known as BCa, is a common tumor that impacts the urinary system. It is marked by a significant fatality rate and an unfavorable outlook. Promising antineoplastic properties are exhibited by brusatol, which is obtained from the dried ripe fruit of Brucea javanica. The present study aimed to evaluate the influence of brusatol on the advancement of BCa and uncover the molecular mechanism involved. Materials and methods We used Cell Counting Kit-8, colony formation and EdU assays to detect cell activity and degree of apoptosis. We used transwell migration assay to detect cell migration and invasion ability. The mechanism of brusatol inhibition of BCa proliferation was studied by flow cytometry, western blotting. Results It was revealed that brusatol could reduce the viability and proliferation of BCa cells. A transwell migration assay revealed that brusatol was able to attenuate the invasion and migration of BCa cells. In addition, treatment with RSL3 or ferrostatin-1 enhanced or reversed the brusatol-induced inhibition of BCa cells. While testing for indicators related to iron death it was determined that treatment with brusatol increased the levels of reactive oxygen species, malondialdehyde and Fe2+ in BCa cells. Mechanistically, brusatol induced ferroptosis by upregulating the expression of ChaC glutathione-gpecific gamma-glutamylcyclotransferase (Chac1) in BCa cells. Moreover, treatment with brusatol significantly suppressed the tumor growth in nude mice. Conclusions To summarize, the findings of this research demonstrated that brusatol hindered the growth of BCa and triggered ferroptosis by increasing the expression of Chac1. Brusatol has the potential to be considered as a promising candidate for treating BCa.