4.4 Article

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

期刊

CANCER CHEMOTHERAPY AND PHARMACOLOGY
卷 85, 期 4, 页码 699-709

出版社

SPRINGER
DOI: 10.1007/s00280-020-04052-w

关键词

Britanin; Pancreatic cancer; Nuclear factor-kappa b; Bioluminescence imaging

资金

  1. National Natural Science Foundation of China [81801863]
  2. Natural Science Basic Research Program of Shaanxi [2019JQ-485]
  3. Research Project of Education Department of Shaanxi Provincial Government of Shaanxi Province of China [18JK0679]
  4. Science and Technology Innovation Base-Open and Sharing Platform of Science and Technology Resources Project of Shaanxi Province [2019PT-26]
  5. Research Foundation of Shaanxi Provincial Research Center for the Project of Prevention and Treatment of Respiratory Diseases [2017GCKF02]

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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.

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