通过新刺激-交换器1作为抗癌剂的真菌二元性香
Guolong Zhou1, Kemin Dong2, Xiaoyuan Xu2
1Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, 266071, People's Republic of China.
European journal of medicinal chemistry
|March 28, 2025
概括
天然的桑二聚体 (Xds) 显示出强大的抗癌作用,特别是对胃癌和黑色素瘤. 这些化合物向Na+/Ca2+交换器1 (NCX1) 和信号通路,导致癌细胞死亡.
科学领域:
- 自然产品化学 自然产品化学
- 癌症生物学 癌症生物学
- 分子药理学分子药理学
背景情况:
- 自然产品可以调节离子通道以抑制癌细胞生长.
- 赞二聚体 (Xds) 是一种具有潜在抗癌性能的天然化合物.
研究的目的:
- 为了分离和表征新的桑二元体.
- 评估Xds对胃癌 (GC) 和黑色素瘤的抗癌活性.
- 阐明Xds在癌细胞中的作用机制.
主要方法:
- 通过共同培养和化学转换,分离和表征18个桑二次体 (Xds).
- 棉花效应分析和化学通信,以确定绝对配置.
- 针对GC和黑色素瘤细胞系的体外细胞毒性测定,体内研究和机械学研究.
主要成果:
- 鉴定出了五种新的桑二元体 (H,I,J-L二元体).
- 八个Xds对AGS胃癌细胞系表现出显著的细胞毒性作用,表现优于西斯.
- 化合物4 (12-O-deacetyl-phomoxanthone A) 激活了Na+/Ca2+交换器1 (NCX1),增加了细胞内Ca2+并抑制PI3K/AKT/β-catenin通路,导致GC细胞死亡.
- Xds在体外和体内均表现出抗黑色素瘤活性.
结论:
- 赞二聚体是有效的细胞毒剂,可以对抗胃癌和黑色素瘤.
- 抗癌机制涉及NCX1的激活和Ca2+信号通路的调节.
- Xds代表了有前途的天然化合物,可作为抗癌疗法进一步开发.
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