Pacidusin B isolated from Phyllanthus acidus triggers ferroptotic cell death in HT1080 cells

Autor: Guangyu Zhu, Dian Luo, Yueqin Zhao, Zhengrui Xiang, Chao Chen, Na Li, Xiaojiang Hao, Xiao Ding, Yingjun Zhang, Yuhan Zhao
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Natural Products and Bioprospecting, Vol 14, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 2192-2195
2192-2209
DOI: 10.1007/s13659-024-00454-y
Popis: Abstract Cancer cells generally exhibit ‘iron addiction’ phenotypes, which contribute to their vulnerability to ferroptosis inducers. Ferroptosis is a newly discovered form of programmed cell death caused by iron-dependent lipid peroxidation. In the present study, pacidusin B, a dichapetalin-type triterpenoid from Phyllanthus acidus (L.) Skeels (Euphorbiaceae), induces ferroptosis in the HT1080 human fibrosarcoma cell line. Cells treated with pacidusin B exhibited the morphological characteristic ‘ballooning’ phenotype of ferroptosis. The biochemical hallmarks of ferroptosis were also observed in pacidusin B-treated cells. Both oxidative stress and ER stress play significant roles in pacidusin B-induced ferroptosis. The activation of the PERK-Nrf2-HO-1 signaling pathway led to iron overload, while inhibition of GPX4 further sensitized cancer cells to ferroptosis. Furthermore, the molecular docking study showed that pacidusin B docked in the same pocket in xCT as the ferroptosis inducer erastin. These results revealed that pacidusin B exerts anticancer effects via inducing ER-mediated ferroptotic cell death. Graphical Abstract
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