乙醇提取物Eclipta prostrata通过Keap1/Nrf2/HO-1轴诱导多发性骨髓瘤铁
Wenxia Li1, Xuejiao Yin2, Hangjie Fu3
1Hangzhou Innovation Institute, Beihang University, Hangzhou, Zhejiang, PR China; Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China.
概括
在多发性骨髓瘤中,Eclipta prostrata提取物通过Keap1/Nrf2/HO-1通路触发铁亡,从而诱导细胞死亡. 这种传统中医药在治疗这种无法治愈的血液癌症方面表现有前途.
科学领域:
- 血液学的恶性瘤
- 传统中国医药 传统中国医药
- 癌症生物学 癌症生物学
背景情况:
- 多发性骨髓瘤 (MM) 是一种无法治愈的血液性恶性瘤,治疗选择有限.
- 中国传统药用植物Eclipta prostrata表现出已知的抗瘤特性.
- 在多发性骨髓瘤中E. prostrata的治疗潜力仍然未被探索.
研究的目的:
- 阐明E. prostrata (EEEP) 的乙醇提取物在多发性骨髓瘤中具有治疗作用的机制.
- 确定EEEP中负责其抗髓瘤活性的关键活性成分.
主要方法:
- 研究了EEEP对MM细胞系 (RPMI-8226,U266) 的亲铁性作用,评估了细胞死亡,增殖,铁积累和脂质过氧化.
- 分析了Keap1/Nrf2/HO-1通路 (Nrf2,Keap1,HO-1,GPX4) 中的关键蛋白质的表达,并使用了西式涂抹.
- 在MM异种移植小鼠模型中评估EEEP的体内疗效,并使用HPLC和UPLC-Q/TOF-MS确定主要成分.
主要成果:
- EEEP在体外和体内都显示出显著抑制MM细胞生长和诱导细胞死亡.
- 通过促进脂质过氧化,甲和Fe2+积累,以及抑制GSH,EEEP在MM细胞中触发了铁亡.
- EEEP调节了Keap1/Nrf2/HO-1轴,通过Nrf2激活,其对脂质过氧化和马隆迪甲积累的影响被逆转.
结论:
- EEEP有效地抑制多发性骨髓瘤的生长,并通过铁亡诱导细胞死亡,由Keap1/Nrf2/HO-1途径介导.
- 已识别的EEEP的关键成分,包括甲基二甲和二甲,可能是其抗髓瘤作用的原因.
- 这项研究强调EEEP是多发性骨髓瘤的新疗法候选者,通过独特的铁灭调节轴起作用.
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