新型厚朴酚衍生物的半合成及体外抗癌作用对人肝癌SMMC-7721细胞增殖、凋亡、迁移和侵袭的影响。
Semisynthesis and in Vitro Anti-cancer Effect of New Magnolol Derivatives on the Cell Proliferation, Apoptosis, Migration, and Invasion of Human Hepatocellular Carcinoma SMMC-7721 Cells.
发表日期:2023
作者:
Na-Na He, Jian-An Wang, Di Huang, Xiao-Long Sun, Feng Ding, Long Zhao, Yu-Xin Zhang, Hong-Mei Li, Cheng-Zhu Wu
来源:
Protein & Cell
摘要:
合成了四种新的厚朴酚衍生物并评估了它们的体外抗癌特性。其中,化合物3对SMMC-7721、SUN-449和HepG2人肝癌细胞系表现出最强的细胞毒活性,IC50值分别为3.39、4.11和6.88μM。化合物3还通过下调Bcl-2和Akt蛋白水平、上调Bax蛋白水平以及裂解caspase-9和-3来诱导SMMC-7721细胞凋亡。此外,Transwell 实验表明,化合物 3 显着抑制 SMMC-7721 细胞的迁移和侵袭,这一点通过下调缺氧诱导因子-1α (HIF-1α)、基质金属蛋白酶-2 和 -9 得到证实。 MMP-2 和 MMP-9) 蛋白质水平。
Four new magnolol derivatives were synthesized and evaluated for their in vitro anti-cancer properties. Among these, compound 3 showed the most potent cytotoxic activity against the SMMC-7721, SUN-449, and HepG2 human hepatocellular carcinoma cell lines, with IC50 values of 3.39, 4.11, and 6.88 µM, respectively. Compound 3 also induced apoptosis of SMMC-7721 cells by down-regulating Bcl-2 and Akt protein levels, up-regulating of Bax protein level, and cleaving caspase-9 and -3. In addition, transwell assays showed that compound 3 significantly suppressed the migration and invasion of SMMC-7721 cells, which was confirmed based on the down-regulation of hypoxia inducible factor-1α (HIF-1α), matrix metalloproteinase-2 and -9 (MMP-2, and MMP-9) protein levels.