Britanin Exhibits Potential Inhibitory Activity on Human Prostate Cancer Cell Lines Through PI3K/Akt/NF-κB Signaling Pathways

Qi Zeng; Yun Zeng; Xu Nie; Yingying Guo; Yonghua Zhan

doi:10.1055/a-1211-4656

Planta Medica, Table of Contents

Planta Med 2020; 86(18): 1401-1410
DOI: 10.1055/a-1211-4656

Biological and Pharmacological Activity

Original Papers

Britanin Exhibits Potential Inhibitory Activity on Human Prostate Cancer Cell Lines Through PI3K/Akt/NF-κB Signaling Pathways

Qi Zeng‡

Engineering Research Center of Molecular and Neuro Imaging of the Ministry of Education, School of Life Science and Technology, Xidian University, Xiʼan, China

,

Yun Zeng‡

Engineering Research Center of Molecular and Neuro Imaging of the Ministry of Education, School of Life Science and Technology, Xidian University, Xiʼan, China

,

Xu Nie

Engineering Research Center of Molecular and Neuro Imaging of the Ministry of Education, School of Life Science and Technology, Xidian University, Xiʼan, China

,

Yingying Guo

Engineering Research Center of Molecular and Neuro Imaging of the Ministry of Education, School of Life Science and Technology, Xidian University, Xiʼan, China

,

Yonghua Zhan‡

Engineering Research Center of Molecular and Neuro Imaging of the Ministry of Education, School of Life Science and Technology, Xidian University, Xiʼan, China

› Author Affiliations

Abstract

Britanin, a natural pseudoguaiacane sesquiterpene lactone, has significant antioxidant and anti-inflammatory activity, but little is known about its tumor inhibitory activity and the underlying mechanism. Here, we demonstrated in vitro and in vivo that britanin inhibited the growth of human prostate cancer cell lines (PC-3, PC-3-LUC, and DU-145). Through in vitro study, the results showed that britanin significantly decreased cell proliferation, migration, and motility. The moderate toxicity of britanin was determined with an acute toxicity study. A luciferase-labeled animal tumor xenograft model and bioluminescence imaging were applied, combining with biological validation for assessing the tumor progression. In vivo results demonstrated that britanin inhibited the growth of PC-3-LUC. The interleukin-2 level in mice was upregulated by britanin, which indicated that britanin induced antitumor immune activation. In addition, britanin downregulated the expression of nuclear factor (NF)-κB p105/p50, pp65, IκBα, pIκBα, phosphoinositide 3-kinase, pPI3k, Akt (protein kinase B, PKB), and pAkt proteins and upregulated expression of Bax. We discovered that britanin inhibits the growth of prostate cancer cells both in vitro and in vivo by regulating PI3K/Akt/NF-κB-related proteins and activating immunity. These findings shed light on the development of britanin as a promising agent for prostate cancer therapy.

Key words

britanin - prostate cancer - bioluminescence imaging - PI3K/Akt/NF-κB

Full Text

References

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