反氧活性维生素C通过触发细胞内ROS-铁-信号交叉和线粒体功能障碍来抑制人类骨髓瘤的生长
Prajakta Vaishampayan1, Yool Lee2
1Department of Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, 99202, USA.
Redox biology
|July 31, 2024
概括
药理维生素C (VC) 通过反应性氧物种 (ROS) - 铁 - 循环破坏线粒体功能,诱导癌细胞死亡. 这项研究突出了VC的重点.
科学领域:
- 在瘤学瘤学.
- 生物化学 生物化学
- 细胞生物学 细胞生物学
背景情况:
- 药理维生素C (VC) 具有亲氧化性质和选择性诱导癌细胞死亡.
- 复杂的氧化还原特性使得VC在癌症治疗中的作用难以定义.
- 骨髓瘤 (OS) 是一种具有挑战性的骨癌,治疗选择有限.
研究的目的:
- 阐明氧化还原活性维生素C诱导癌细胞死亡的机制.
- 研究细胞内活性氧物种 (ROS),铁和在VC诱导的细胞毒性中的作用.
- 在骨髓瘤模型中评估高剂量VC的治疗潜力.
主要方法:
- 利用2D和3D人类骨髓瘤细胞培养模型.
- 使用活细胞成像,药理学抑制剂 (ferroptosis,apoptosis),遗传抑制和RNA测序.
- 在体内进行的骨髓瘤异种移植研究.
主要成果:
- 只有可氧化形式的VC通过依赖铁的ROS生产诱导剂量依赖的细胞毒性.
- VC通过IP3Rs触发的释放,导致线粒体ROS的产生和非细胞亡的细胞死亡.
- 高剂量的VC在体内减少了瘤的生长,与线粒体ATP合成酶表达的改变有关.
结论:
- 维生素C的氧化还原活性性质对于诱导骨髓瘤细胞死亡至关重要.
- VC通过一种新的ROS-铁-交叉声和线粒体功能障碍途径诱导癌细胞死亡.
- 维生素C通过向线粒体新陈代谢,显示出作为骨髓瘤治疗剂的潜力.
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