人鼻咽癌CNE-2Z细胞中新型本草延胡索衍生物的半合成和抗癌特性.
Semisynthesis and anti-cancer properties of novel honokiol derivatives in human nasopharyngeal carcinoma CNE-2Z cells.
发表日期:2023 Dec
作者:
Bo-Han Li, Hui Ma, Jing Zhu, Jie Chen, Yi-Qun Dai, Xiao-Jing Zhang, Hong-Mei Li, Cheng-Zhu Wu
来源:
J Enzym Inhib Med Ch
摘要:
在本研究中,合成了21种新的红酰木树酚衍生物,并研究了它们的抗癌特性。其中,化合物1g对人鼻咽癌CNE-2Z细胞、人胃癌SGC7901细胞、人乳腺癌MCF-7细胞和小鼠Leydig睾丸癌I-10细胞表现出最强的细胞毒性活性,其IC50值分别为6.04、7.17、6.83和5.30μM。与原始化合物相比,1g对CNE-2Z细胞的细胞毒效果增强了最多5.18倍。我们进一步证明了1g通过下调HIF-1α,MMP-2,MMP-9,Bcl-2,Akt的蛋白水平以及上调Bax的蛋白水平来抑制CNE-2Z细胞的生长,抑制其迁移和侵袭能力并诱导细胞凋亡。转染HIF-1α siRNA的CNE-2Z细胞减少了细胞的迁移和侵袭。此外,在体内实验证实1g对CNE-2Z细胞移植裸鼠的肿瘤生长具有抑制作用且毒性较低。因此,我们的数据表明1g是一种用于鼻咽癌治疗的潜在安全和有效的前导化合物。
In this study, 21 new honokiol derivatives were synthesised, and their anti-cancer properties were investigated. Among these, compound 1g exhibited the most potent cytotoxic activity against human nasopharyngeal carcinoma CNE-2Z cells, human gastric cancer SGC7901 cells, human breast cancer MCF-7 cells, and mouse leydig testicular cancer I-10 lines with IC50 values of 6.04, 7.17, 6.83, and 5.30 μM, respectively. Compared to the parental compound, 1g displayed up to 5.18-fold enhancement of the cytotoxic effect on CNE-2Z cells. We further demonstrated that 1g inhibited cell growth, suppressed migration and invasion, and induced apoptosis of CNE-2Z cells by down-regulating HIF-1α, MMP-2, MMP-9, Bcl-2, Akt and up-regulating Bax protein levels. Transfection of CNE-2Z cells with HIF-1α siRNA reduced cell migration and invasion. In addition, in vivo experiments confirmed that 1g inhibited tumour growth in CNE-2Z cell-xenografted nude mice with low toxicity. Thus, our data suggested that 1g was a potent and safe lead compound for nasopharyngeal carcinoma therapy.