(+)-Strebloside induces Non-Hodgkin lymphoma cell death through the STEAP3-Mediated Ferroptosis and MAPK pathway

Yu Zhao; Jing Cai; Ying Yang; Dongmei Zhang; Jiayi Ren; Shuyun Xiao; Jian Xu; Feng Feng; Rong Wu; Jie Zhang

doi:10.1016/S1875-5364(25)60873-9

Chinese Journal of Natural Medicines ›› 2025, Vol. 23 ›› Issue (10) :1221 -1231. DOI: 10.1016/S1875-5364(25)60873-9

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research-article

(+)-Strebloside induces Non-Hodgkin lymphoma cell death through the STEAP3-Mediated Ferroptosis and MAPK pathway

Yu Zhao ¹^,^∆
, Jing Cai ¹^,^∆
, Ying Yang ¹
, Dongmei Zhang ¹
, Jiayi Ren ¹
, Shuyun Xiao ¹
, Jian Xu ¹
, Feng Feng ¹^,²
, Rong Wu ³^,^*
, Jie Zhang ¹^,^*

Author information +

History +

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Abstract

(+)-Strebloside, a significant bioactive compound isolated from the roots of Streblus asper Lour., demonstrates inhibitory effects against multiple malignancies. However, its specific function and underlying mechanistic pathways in Non-Hodgkin lymphoma (NHL) remain unexplored. This investigation sought to elucidate the role and potential mechanisms of (+)-strebloside-induced NHL cell death. The results demonstrated that (+)-strebloside significantly induced apoptosis and ferroptosis in NHL cells, including those from Raji cell-derived xenograft models. Mechanistic analyses revealed that (+)-strebloside enhanced six-transmembrane epithelial antigen of prostate 3 (STEAP3)-induced ferroptosis in NHL, and STEAP3 inhibition reduced the proliferation-inhibitory effects of (+)-strebloside. Furthermore, (+)-strebloside suppressed NHL proliferation through the mitogen-activated protein kinase (MAPK) pathway, and extracellular signal-regulated kinase (ERK) inhibition diminished the proliferation-inhibitory activity induced by (+)-strebloside. These findings indicate that (+)-strebloside presents promising therapeutic potential for NHL treatment.

Keywords

Non-Hodgkin lymphoma / (+)-Strebloside / Antitumor activity / MAPK / Ferroptosis

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Yu Zhao, Jing Cai, Ying Yang, Dongmei Zhang, Jiayi Ren, Shuyun Xiao, Jian Xu, Feng Feng, Rong Wu, Jie Zhang. (+)-Strebloside induces Non-Hodgkin lymphoma cell death through the STEAP3-Mediated Ferroptosis and MAPK pathway. Chinese Journal of Natural Medicines, 2025, 23(10): 1221-1231 DOI:10.1016/S1875-5364(25)60873-9

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