Department of Hepatobiliary Pancreatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350028, China.
Department of Intensive Care Unit, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350028, China.
J Antibiot (Tokyo). 2024 Jul;77(7):428-435. doi: 10.1038/s41429-024-00732-4. Epub 2024 May 9.
Chalcomoracin (CMR), a Diels-Alder adduct obtained from mulberry leaves, demonstrated wide-spectrum anti-cancer activity. Herein, we aimed to explore the function of CMR and how it works in hepatocellular carcinoma (HCC). Human HCC cell lines Hep3B and SNU-387 were cultured and treated with various concentrations of CMR (1.5, 3, and 6 µM). Subsequently, the effects of CMR on cell viability, colony formation, apoptosis, migration, and invasion abilities were studied in vitro. Furthermore, the levels of endoplasmic reticulum (ER) stress-related proteins and mitogen-activated protein kinase (MAPK) pathway-related proteins in cells under CMR exposure were detected using western blot. Experiments in vivo were conducted to examine the effects of CMR on tumor growth in HCC. CMR administration inhibited the viability and clonogenic, migration, and invasion abilities, as well as promoted cell apoptosis and ER stress in Hep3B and SNU-387 cells. In addition, CMR treatment reduced the phosphorylation levels of ERK, P38, and JNK in the MAPK pathway. Moreover, an in vivo study showed that CMR administration could inhibit tumorigenesis and MAPK pathway activity in HCC. Our data indicate that CMR has the potential to inhibit the development of HCC, potentially through the inhibition of the MAPK pathway. These findings suggest that CMR may have promising applications as an anticancer agent in future therapeutics for HCC.
桑枝中获得的狄尔斯-阿尔德加合物 chalcomoracin（CMR）具有广谱抗癌活性。在此，我们旨在探讨 CMR 的功能及其在肝癌（HCC）中的作用机制。培养人肝癌细胞系 Hep3B 和 SNU-387，并使用不同浓度的 CMR（1.5、3 和 6 μM）处理这些细胞。然后，在体外研究 CMR 对细胞活力、集落形成、细胞凋亡、迁移和侵袭能力的影响。此外，通过 Western blot 检测 CMR 暴露下细胞中内质网（ER）应激相关蛋白和丝裂原激活蛋白激酶（MAPK）通路相关蛋白的水平。进行体内实验以研究 CMR 对 HCC 肿瘤生长的影响。CMR 给药抑制 Hep3B 和 SNU-387 细胞的活力和集落形成、迁移和侵袭能力，并促进细胞凋亡和 ER 应激。此外，CMR 处理降低了 MAPK 通路中 ERK、P38 和 JNK 的磷酸化水平。此外，体内研究表明 CMR 给药可抑制 HCC 中的肿瘤发生和 MAPK 通路活性。我们的数据表明，CMR 具有抑制 HCC 发展的潜力，可能是通过抑制 MAPK 通路。这些发现表明，CMR 可能在未来 HCC 的治疗中作为一种抗癌药物具有广阔的应用前景。
