Novel Hybrids of Podophyllotoxin and Coumarin Inhibit the Growth and Migration of Human Oral Squamous Carcinoma Cells.

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 inhibited the proliferation of three human oral squamous carcinoma cell lines with nanomolar IC values, as well as displayed less toxicity on normal cells. Mechanistic studies indicated that triggered HSC-2 cell apoptosis, induced cell cycle arrest, and inhibited cell migration. Moreover, could disturb the microtubule network via binding into the tubulin. It was noteworthy that induction of autophagy by was associated with the upregulation of Beclin1, as well as LC3-II. Furthermore, significantly stimulated the AMPK pathway and restrained the AKT/mTOR pathway in HSC-2 cells. These results indicated that compound was a promising candidate for further investigation.