Capsaicin: A "hot" KDM1A/LSD1 inhibitor from peppers
Capsaicin: A "hot" KDM1A/LSD1 inhibitor from peppers
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DOI：
10.1016/j.bioorg.2020.104161
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发表时间：
2020-10-01
影响因子：
5.1
通讯作者：
Song, Zhiyu
中科院分区：
文献类型：
--
作者：
Jia, Gang;Cang, Shundong;Song, Zhiyu
辣椒素是植物次生代谢产物，辣椒碱是辣椒产生辣味的主要成分，作为食品添加剂应用广泛。辣椒素是赖氨酸特异性脱甲基酶1A（KDM 1A/LSD 1）的抑制剂，在生化水平上的IC_（50）为0.6 ± 0.0421 μ M，并能与KDM 1A重组体直接可逆结合。进一步的细胞研究证实辣椒素可以结合并抑制胃癌细胞株BGC-823中的KDM 1A，并通过逆转上皮间质转化（EMT）进一步抑制细胞的侵袭和迁移。综上所述，我们的研究发现KDM 1A是辣椒素的作用靶点，并首次揭示了辣椒素作为组蛋白甲基化修饰剂的作用，这可能为进一步优化KDM 1A抑制剂提供新的骨架。
Capsaicinoids are plant secondary metabolites, and capsaicin is the main principal that responsible to the pungency of chili peppers, with widely application as food additive. In our study, capsaicin was characterized as lysine specific demethylase 1A (KDM1A/LSD1) inhibitor with IC50 of 0.6 +/- 0.0421 mu M in biochemical level, and can bind KDM1A recombinant directly and reversibly. Further cellular study confirmed that capsaicin can bind and inhibit KDM1A in gastric cancer cell line BGC-823 and further inhibit cell invasion and migration by reversing epithelial-mesenchymal transition (EMT). In sum, our findings identified KDM1A as a target of capsaicin and reveals capsaicin as a modifier of histone methylation for the first time, which may provide a new skeleton for further optimization of KDM1A inhibitor.