A novel natural product, britanin, inhibits tumor growth of pancreatic cancer by suppressing nuclear factor-kappa B activation

Pancreatic cancer has a high mortality rate and poor prognosis. The development of novel medicines for pancreatic cancer therapy is urgently need. Britanin is a bioactive sesquiterpene lactone, that exhibits excellent anti-inflammatory and antioxidant effects. However, the potential anti-tumour activity of britanin is also considerable. Hence, in this study, the in vitro and in vivo anti-pancreatic cancer effects of britanin were investigated. Several pancreatic cancer cell lines were applied to evaluate inhibition of proliferation, migration and NF-kappa B pathway in vitro. Then in vivo toxicity of britanin was evaluated in BALB/c mice. The in vivo inhibitory effects of britanin were investigated by bioluminescence imaging, traditional methods and histological analysis in a pancreatic cancer xenograft mouse model. The results showed that britanin exhibited effective anti-tumour actions both in vitro and in vivo. The IC50 values in PANC-1, BxPC-3 and MIA CaPa-2 cell lines were 1.348, 3.367 and 3.104 mu mol/L, respectively, and cell proliferation and migration were significantly inhibited by britanin treatment. Western blotting demonstrated that NF-kappa B family proteins, such as P50, P65, and P-P65 were affected by britanin treatment. It is worth noting that the P-P65 protein, which regulates the expression of multiple factors downstream, was significantly decreased in britanin treated group. In vivo experiments verified that britanin could suppress the tumour progression in a pancreatic cancer xenograft mouse model, while the compound did not exhibit intolerable toxicity. In conclusion, britanin has remarkable potential treatment effects against pancreatic cancer, and it could be developed as a new agent for pancreatic cancer chemotherapy.