(+)-Strebloside induces Non-Hodgkin’s lymphoma cell death through the STEAP3-mediated ferroptosis and MAPK pathway

(+)-Strebloside, a notable bioactive compound isolated from the roots of Streblus asper Lour., exhibits inhibitory effects on various malignancies. However, its specific role and potential mechanistic pathways in Non-Hodgkin’s lymphoma (NHL) have not been previously reported. This study aimed to investigate the role and potential mechanisms of (+)-strebloside-induced NHL cell death. The findings showed that (+)-strebloside notably triggered apoptosis and ferroptosis in NHL cells, including those from Raji cell-derived xenograft models. Mechanistic studies revealed that (+)-strebloside could upregulate STEAP3-induced ferroptosis in NHL, and the inhibition of STEAP3 mitigated the proliferation-inhibitory effects of (+)-strebloside. Additionally, (+)-strebloside inhibited NHL proliferation through the MAPK pathway, and the inhibition of ERK further alleviated the proliferation-inhibitory activity induced by (+)-Strebloside. In conclusion, these findings suggest the promising potential of (+)-strebloside in the treatment of NHL.