Novel Hybrids of Podophyllotoxin and Coumarin Inhibit the Growth and Migration of Human Oral Squamous Carcinoma Cells
文献类型： 外文期刊
作者： Bai, Guohui 1 ; Zhao, Dan 1 ; Ran, Xin 1 ; Zhang, Lei 3 ; Zhao, Degang 1 ;
作者机构： 1.Guizhou Univ, Inst Agrobioengn, Minist Educ, Key Lab Plant Resources Conservat & Germplasm Inn, Guiyang, Peoples R China
2.Guizhou Univ, Coll Life Sci, Guiyang, Peoples R China
3.Zunyi Med Univ, Key Lab Biocatalysis & Chiral Drug Synth Guizhou, Zunyi, Guizhou, Peoples R China
4.Zunyi Med Univ, Sch Pharm, Zunyi, Guizhou, Peoples R China
5.Guizhou Acad Agr Sci, Inst Guizhou Distinct Plant Resources Conservat, Guiyang, Peoples R China
关键词： podophyllotoxin; coumarin; hybrid strategy; human oral squamous carcinoma cells; anticancer; molecular mechanism
期刊名称：FRONTIERS IN CHEMISTRY （ 影响因子：5.221； 五年影响因子：5.385 ）
ISSN： 2296-2646
年卷期： 2021 年 8 卷
页码：
收录情况： SCI
摘要： Oral squamous cell carcinoma is the most common malignancy of oral tumor. In this study, two novel hybrids of podophyllotoxin and coumarin were designed using molecular hybridization strategy and synthesized. Pharmacological evaluation showed that the potent compound 12b inhibited the proliferation of three human oral squamous carcinoma cell lines with nanomolar IC50 values, as well as displayed less toxicity on normal cells. Mechanistic studies indicated that 12b triggered HSC-2 cell apoptosis, induced cell cycle arrest, and inhibited cell migration. Moreover, 12b could disturb the microtubule network via binding into the tubulin. It was noteworthy that induction of autophagy by 12b was associated with the upregulation of Beclin1, as well as LC3-II. Furthermore, 12b significantly stimulated the AMPK pathway and restrained the AKT/mTOR pathway in HSC-2 cells. These results indicated that compound 12b was a promising candidate for further investigation.
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