1. Artemisinin and its derivatives can significantly inhibit lung tumorigenesis and tumor metastasis through Wnt/β-catenin signaling.
- Author
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Tong Y, Liu Y, Zheng H, Zheng L, Liu W, Wu J, Ou R, Zhang G, Li F, Hu M, Liu Z, and Lu L
- Subjects
- A549 Cells, Animals, Antimalarials chemistry, Antimalarials pharmacology, Artemisinins chemistry, Artesunate, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung metabolism, Cell Cycle Checkpoints drug effects, Cell Line, Cell Line, Tumor, Cell Proliferation drug effects, Cell Transformation, Neoplastic drug effects, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic metabolism, Female, Humans, Lung Neoplasms genetics, Lung Neoplasms metabolism, Mice, Inbred BALB C, Mice, Nude, Neoplasm Metastasis, RNA Interference, Wnt Signaling Pathway genetics, Xenograft Model Antitumor Assays, beta Catenin genetics, Artemisinins pharmacology, Carcinoma, Non-Small-Cell Lung prevention & control, Lung Neoplasms prevention & control, Wnt Signaling Pathway drug effects, beta Catenin metabolism
- 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., Competing Interests: The authors declare that they have no conflict of interest.
- Published
- 2016
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