Pristimerin induces apoptosis and autophagy via activation of ROS/ASK1/JNK pathway in human breast cancer in vitro and in vivo

• Published in: Cell death discovery Vol. 5; no. 1; pp. 125 - 13
• Main Authors: Zhao, Qun, Liu, Yingxiang, Zhong, Jing, Bi, Yun, Liu, Yongqiang, Ren, Ziting, Li, Xiang, Jia, Junjun, Yu, Mengting, Yu, Xianjun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05-08-2019; Springer Nature B.V
• Subjects: 631/154/436; 631/67/1347; Acetylcysteine; Antitumor activity; Apoptosis; Autophagy; Biochemistry; Biomedical and Life Sciences; Breast cancer; Cell Biology; Cell cycle; Cell Cycle Analysis; Cell death; Life Sciences; MAP kinase; Phagocytosis; Phosphorylation; Reactive oxygen species; Signal transduction; Stem Cells; Thioredoxin; Xenografts; Breast cancer; Pharmacology
• ISSN: 2058-7716; 2058-7716
• DOI: 10.1038/s41420-019-0208-0

Breast cancer is the most common malignant tumor in women, and progress toward long-term survival has stagnated. Pristimerin, a natural quinonemethide triterpenoid, exhibits potential anti-tumor effects on various cancers. However, the underlying mechanism remains poorly understood. In this study, we found that pristimerin reduced the viability of breast cancer cells in vitro and the growth of xenografts in vivo, and these reductions were accompanied by thioredoxin-1 (Trx-1) inhibition and ASK1 and JNK activation. The results showed that pristimerin inhibited cell cycle progression and triggered cell apoptosis and autophagy. Furthermore, we found that the generation of reactive oxygen species (ROS) was a critical mediator in pristimerin-induced cell death. Enhanced ROS generation by pristimerin activated the ASK1/JNK signaling pathway. Inhibition of ROS with N-acetyl cysteine (NAC) significantly decreased pristimerin-induced cell death by inhibiting the phosphorylation of ASK1 and JNK. Taken together, these results suggest a critical role for the ROS/ASK1/JNK pathway in the anticancer activity of pristimerin.