海洋类利帕丁E和H诱导癌症化学疗法的铁亡
Wenjun Wang1,2, Foqing Ma1, Yuen Tsz Cheung1
1Department of Chemistry, The Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Kowloon, Hong Kong 999077, China.
Journal of medicinal chemistry
|August 14, 2023
概括
海洋化物勒帕丁斯E和H被确定为新型铁灭菌诱导剂. 这些化合物通过通过p53-SLC7A11-GPX4通路促进铁亡,具有极小的毒性,显示出强大的抗癌活性.
科学领域:
- 海洋天然产品 海洋天然产品
- 癌症治疗方法 癌症治疗方法
- 细胞死亡途径的细胞死亡途径.
背景情况:
- 诱导铁死是一种有前途的癌症治疗策略.
- 新型铁灭菌诱导剂的开发是有限的.
- 海洋化物是治疗剂的未充分探索的来源.
研究的目的:
- 为了识别和描述来自海洋来源的新的铁灭诱导剂.
- 阐明新型海洋类化合物的作用机制.
- 评估已识别的化合物的体内抗癌疗效和安全性.
主要方法:
- 在体外细胞毒性测定.
- 对活性氧物种 (ROS) 和脂质过氧化物进行分析.
- 对关键与铁亡相关的蛋白质 (p53,SLC7A11,GPX4,ACSL4) 的西部斑点分析.
- 在动物模型中进行体内抗瘤疗效研究.
主要成果:
- 勒帕丁E和H被确定为新的铁灭诱导剂.
- 已证明细胞毒性,增加ROS和脂质过氧化物,以及改变蛋白质表达 (p53,SLC7A11,GPX4,ACSL4) 在体外.
- 勒帕丁E和H通过p53-SLC7A11-GPX4通路诱导铁.
- 勒帕丁H在体内显示出显著的抗瘤疗效,毒性低.
结论:
- 海洋化物勒帕丁E和H代表了一个新的类型的ferroptosis诱导剂.
- 这些化合物向了经典的p53-SLC7A11-GPX4铁亡途径.
- 勒帕丁E和H具有抗癌治疗的翻译潜力.
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