库库比他辛E通过增强反应性氧物种调节的线粒体功能障碍和内分泌网膜应激作用,引起喉平细胞癌的亡
Xucai Zheng1,2, Puze Tang3, Hui Li4
1Department of Oncology, The Second Hospital of Anhui Medical University Hefei 230601, Anhui, China.
American journal of cancer research
|September 13, 2024
概括
库库比他E (CuE) 在治疗喉状细胞癌 (LSCC) 方面表现有前途. 这种天然化合物降低了癌细胞的活力,并通过反应性氧物种 (ROS) 介导的线粒体和内质网膜压力触发了亡.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 自然产品 化学 化学
背景情况:
- 喉平细胞癌 (LSCC) 是一个重大的全球健康挑战,治疗选择有限.
- 鉴定LSCC的新型治疗剂是非常重要的,因为发病率和死亡率不断上升.
- 库库比他E (CuE) 是一种天然的三类化合物,已显示出抗癌性质,但其在LSCC中的有效性和机制尚未被探索.
研究的目的:
- 调查Cucurbitacin E (CuE) 的抗LSCC作用.
- 阐明CuE在LSCC细胞中作用的分子机制.
- 评估CuE作为喉癌的潜在治疗候选者.
主要方法:
- 在体外研究评估LSCC细胞活力和亡.
- 线粒体膜潜力,细胞染色体c释放和卡斯帕酶激活测试.
- 细胞内膜网膜 (ER) 应激路径分析 (PERK/eIF2a/ATF4/CHOP).
- 反应性氧物种 (ROS) 水平测量和N-乙半氨酸 (NAC) 救援实验.
- 使用小鼠LSCC模型的体内研究.
主要成果:
- CuE显著降低了LSCC细胞活力,并在体外诱导了亡.
- 通过降低线粒体膜潜力并增加分裂的caspase-3和PARP,CuE触发了线粒体依赖的亡.
- 通过PERK/eIF2a/ATF4/CHOP通路,CuE诱导了ER压力,导致LSCC细胞亡.
- CuE提高了细胞内ROS水平,这对于调解线粒体功能障碍,ER压力和亡至关重要.
- 在小鼠LSCC模型中,CuE表现出类似的抗瘤作用.
结论:
- CuE抑制LSCC的增殖,并通过ROS调节的线粒体功能障碍和ER压力诱导亡.
- CuE代表了一种有前途的天然化合物,用于开发新的喉癌疗法.
- 针对ROS,线粒体通路和ER压力可能是LSCC治疗的有效策略.
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