DOI: 10.1002/ame2.12521
Brassinin from Brassica campestris L.inhibits colorectal cancer by inducing p62/NRF2/GPX4-regulated ferroptosis
Shi-Yuan Wen1
Rui-Rui Gao2
Yan-Yan Chen3
Yi-Jie Wang2
Xin-Tong Wang2
Hai-Xin Liu2
1.College of Basic Medical Sciences,Shanxi Medical University,Taiyuan,China2.College of Traditional Chinese Medicine and Food Engineering,Shanxi University of Chinese Medicine,Taiyuan,China3.School of Medicine,Jiangsu University,Zhenjiang,China
摘要：Background:Indole phytoalexins,plant-derived compounds present in cruciferous vegetables,have demonstrated anticancer properties.Brassinin(BSN),derived from Brassica campestris L.var.campestris,is known for its potent antitumor effects on various cancers.However,the role of ferroptosis in regulating the antitumor effects of BSN has not been fully elucidated.
Methods:The components of B.campestris L.against colorectal cancer(CRC)were analyzed by network pharmacology.CCK-8 assay and colony formation assay de-tected cell viability induced by BSN.Molecular docking verified the binding of BSN to the target protein.Western blot and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)assay revealed whether BSN can inactivate the NRF2 sign-aling and inhibit the expression of p62 and HO-1.The RKO-xenograft tumor models were established and then were treated by 75 or 150 mg/kg BSN to verify the antitu-mor efficacy and side effects of BSN.
Results:Network pharmacology suggested that BSN is the most important compo-nent of B.campestris L.against CRC.BSN inhibits CRC cell viability in a dose-and time-dependent manner.Furthermore,this inhibitory effect is associated with the in-duction of ferroptosis,as BSN suppresses the cell viability of CRC by inducing GPX4-regulated ferroptosis.BSN may bind to NRF2 protein to inactivate the NRF2 signaling,inhibiting the expression of p62 and HO-1.Importantly,a low dose or a high dose of BSN significantly reduced the tumor growth in vivo.
Conclusions:Our findings reveal that BSN blocks CRC growth by inducing p62/NRF2/GPX4-regulated ferroptosis,which may be a novel lead compound for tumor treatment.
机标关键词：ferroptosisbrassicacancerfrombrassinincampestriscolorectalgpx4-regulated
论文发表日期：2025-07-30
在线出版日期：2025-09-28（本平台首次上网日期，不代表文献的发表时间）
页数：11( 1155-1165 )
英文信息