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(-)-β-hydrastine Suppresses the Proliferation and Invasion of Human Lung Adenocarcinoma Cells by Inhibiting PAK4 Kinase Activity

(-)-β-hydrastine Suppresses the Proliferation and Invasion of Human Lung Adenocarcinoma Cells by Inhibiting PAK4 Kinase Activity

Bingyu Guo, Xiaodong Li, Shuai Song, Meng Chen, Maosheng Cheng, Dongmei Zhao, Feng Li

Oncol Rep. 2016 Apr;35(4):2246-56.

PMID: 26821251

Abstract:

(-)-β-hydrastine is one of the main active components of the medicinal plant, Hydrastis canadensis, which is used in many dietary supplements intended to enhance the immune system. However, whether (-)-β-hydrastine affects the tumor signaling pathway remains unexplored. In the present study, we found that (-)-β-hydrastine inhibited the kinase activity of p21-activated kinase 4 (PAK4), which is involved in the regulation of cytoskeletal reorganization, cell proliferation, gene transcription, oncogenic transformation and cell invasion. In the present study, (-)-β-hydrastine suppressed lung adenocarcinoma cell proliferation by inhibiting expression of cyclin D1/D3 and CDK2/4/6, leading to cell cycle arrest at the G1 phase, in a PAK4 kinase-dependent manner. Moreover, inhibition of PAK4 kinase activity by (-)-β-hydrastine also promoted the early apoptosis of lung adenocarcinoma cells through the mitochondrial apoptosis pathway. In addition, (-)-β-hydrastine significantly suppressed the migration and invasion of human lung adenocarcinoma cells in conjunction with concomitant blockage of the PAK4/LIMK1/cofilin, PAK4/SCG10 and PAK4/MMP2 pathways. All of these data indicate that (-)-β-hydrastine, as a novel PAK4 inhibitor, suppresses the proliferation and invasion of lung adenocarcinoma cells. Taken together, these results provide novel insight into the development of a PAK4 kinase inhibitor and a potential therapeutic strategy for lung cancer.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP118081	Hydrastine		118-08-1	Price

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