Oncotarget

Research Papers:

Artemisinin and its derivatives can significantly inhibit lung tumorigenesis and tumor metastasis through Wnt/β-catenin signaling

Yunli Tong _, Yuting Liu, Hongming Zheng, Liang Zheng, Wenqin Liu, Jinjun Wu, Rilan Ou, Guiyu Zhang, Fangyuan Li, Ming Hu, Zhongqiu Liu and Linlin Lu

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Oncotarget. 2016; 7:31413-31428. https://doi.org/10.18632/oncotarget.8920

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Abstract

Yunli Tong1,2,*, Yuting Liu1,2,*, Hongming Zheng2, Liang Zheng1,2, Wenqin Liu1,2, Jinjun Wu2, Rilan Ou2, Guiyu Zhang2, Fangyuan Li2, Ming Hu2,3, Zhongqiu Liu1,2, Linlin Lu2

1School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China

2International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China

3Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, 77030, USA

*These authors have contributed equally to this work

Correspondence to:

Zhongqiu Liu, e-mail: liuzq@gzucm.edu.cn, liuzq@smu.edu.cn

Linlin Lu, e-mail: lllu@gzucm.edu.cn

Keywords: non-small-cell lung cancer, artemisinin, derivative, Wnt/β-catenin

Received: November 16, 2015    Accepted: April 02, 2016    Published: April 22, 2016

ABSTRACT

Non-small-cell lung cancer (NSCLC) is the most prevalent malignancy worldwide given its high incidence, considerable mortality, and poor prognosis. The anti-malaria compounds artemisinin (ART), dihydroartemisinin (DHA), and artesunate (ARTS) reportedly have anti-cancer potential, although the underlying mechanisms remain unclear. In this work, we used flow cytometry to show that ART, DHA, and ARTS could inhibit the proliferation of A549 and H1299 cells by arresting cell cycle in G1 phase. Meanwhile, tumor malignancy including migration, invasion, cancer stem cells, and epithelial–mesenchymal transition were also significantly suppressed by these compounds. Furthermore, ART, DHA, and ARTS remarkably decreased tumor growth in vivo. By using IWP-2, the inhibitor of Wnt/β-catenin pathway, and Wnt5a siRNA, we found that ART, DHA, and ARTS could render tumor inhibition partially dependent on Wnt/β-catenin inactivation. These compounds could strikingly decrease the protein level of Wnt5-a/b and simultaneously increase those of NKD2 and Axin2, ultimately resulting in β-catenin downregulation. In summary, our findings revealed that ART, DHA, and ARTS could suppress lung-tumor progression by inhibiting Wnt/β-catenin pathway, thereby suggesting a novel target for ART, DHA, and ARTS in cancer treatment.


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