Wen Shi-Yuan, Gao Rui-Rui, Chen Yan-Yan, Wang Yi-Jie, Wang Xin-Tong, Liu Hai-Xin
College of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China.
College of Traditional Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Taiyuan, China.
Animal Model Exp Med. 2025 Jul;8(7):1155-1165. doi: 10.1002/ame2.12521. Epub 2025 Jan 23.
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.
The components of B. campestris L. against colorectal cancer (CRC) were analyzed by network pharmacology. CCK-8 assay and colony formation assay detected 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 signaling 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 antitumor efficacy and side effects of BSN.
Network pharmacology suggested that BSN is the most important component 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 induction 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.
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.
吲哚类植物抗毒素是十字花科蔬菜中含有的植物源化合物，已显示出抗癌特性。源自油菜的油菜素（BSN）以其对多种癌症的强大抗肿瘤作用而闻名。然而，铁死亡在调节BSN抗肿瘤作用中的作用尚未完全阐明。
采用网络药理学分析油菜对结直肠癌（CRC）的成分。CCK-8法和集落形成试验检测BSN诱导的细胞活力。分子对接验证了BSN与靶蛋白的结合。蛋白质免疫印迹法和逆转录定量聚合酶链反应（RT-qPCR）检测BSN是否能使NRF2信号失活并抑制p62和HO-1的表达。建立RKO异种移植肿瘤模型，然后用75或150mg/kg BSN处理，以验证BSN的抗肿瘤疗效和副作用。
网络药理学表明，BSN是油菜抗CRC的最重要成分。BSN以剂量和时间依赖性方式抑制CRC细胞活力。此外，这种抑制作用与铁死亡的诱导有关，因为BSN通过诱导GPX4调节的铁死亡来抑制CRC的细胞活力。BSN可能与NRF2蛋白结合，使NRF2信号失活，抑制p62和HO-1的表达。重要的是，低剂量或高剂量的BSN均能显著降低体内肿瘤生长。
我们的研究结果表明，BSN通过诱导p62/NRF2/GPX4调节的铁死亡来阻断CRC的生长，这可能是一种新型的肿瘤治疗先导化合物。
