Deltonin induced both apoptosis and autophagy in head and neck squamous carcinoma FaDu cell
Abstract:
For decades, despite the advancement of medical science, the prognosis of head and neck squamous cell carcinoma (HNSCC), has not improved. Deltonin is one of the major active components of Dioscorea Zingiberensis Wright that has been used for anthrax, rheumatic heart disease, rheumatoid arthritis etc. By employing HNSCC FaDu cell and normal human epidermal keratinocyte, we investigate deltonin efficacy and associated mechanism in both cell culture and nude mice xenografts. Deltonin treatment selectively prevents proliferation of FaDu cells by cell-cycle arrest and induction of apoptosis, via activating checkpoint kinase Chk1and Chk2 as well as caspases 8, 9 and 3. Meanwhile, we found that treatment with deltonin induced autophagy, which played a protective role against deltonin-induced apoptosis. Further studies revealed that deltonin activated autophagy by Akt-mTOR signaling. Additionally, xenograft model showed that administration of deltonin significantly inhibited tumor growth and prolonged survival of tumor bearing mice. Our studies suggested that deltonin might be a potential chemotherapeutic agent against HNSCC, which might contribute to clinical application and pharmacological study of deltonin in future anti-cancer research.