Xanthohumol inhibits non-small cell lung cancer via directly targeting T-lymphokine-activated killer cell-originated protein kinase
Shuang Zhao
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorJinling Cui
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorLixing Cao
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorKai Han
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorXuan Ma
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorHui Chen
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorShutao Yin
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorChong Zhao
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorCorresponding Author
Changwei Ma
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Correspondence
Hongbo Hu and Changwei Ma, College of Food Science and Nutritional Engineering, China Agricultural University, No. 17 Qinghua East Road, Haidian District, Beijing 100083, China.
Email: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Hongbo Hu
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Correspondence
Hongbo Hu and Changwei Ma, College of Food Science and Nutritional Engineering, China Agricultural University, No. 17 Qinghua East Road, Haidian District, Beijing 100083, China.
Email: [email protected]; [email protected]
Search for more papers by this authorShuang Zhao
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorJinling Cui
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorLixing Cao
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorKai Han
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorXuan Ma
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorHui Chen
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorShutao Yin
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorChong Zhao
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Search for more papers by this authorCorresponding Author
Changwei Ma
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Correspondence
Hongbo Hu and Changwei Ma, College of Food Science and Nutritional Engineering, China Agricultural University, No. 17 Qinghua East Road, Haidian District, Beijing 100083, China.
Email: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Hongbo Hu
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Correspondence
Hongbo Hu and Changwei Ma, College of Food Science and Nutritional Engineering, China Agricultural University, No. 17 Qinghua East Road, Haidian District, Beijing 100083, China.
Email: [email protected]; [email protected]
Search for more papers by this authorAbstract
Xanthohumol is a principal prenylated chalcone isolated from hops. Previous studies have shown that xanthohumol was effective against various types of cancer, but the mechanisms, especially the direct targets for xanthohumol to exert an anticancer effect, remain elusive. Overexpression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) promotes tumorigenesis, invasion and metastasis, implying the likely potential for targeting TOPK in cancer prevention and treatment. In the present study, we found that xanthohumol significantly inhibited the cell proliferation, migration and invasion of non-small cell lung cancer (NSCLC) in vitro and suppressed tumor growth in vivo, which is well correlated with inactivating TOPK, evidenced by reduced phosphorylation of TOPK and its downstream signaling histone H3 and Akt, and decreased its kinase activity. Moreover, molecular docking and biomolecular interaction analysis showed that xanthohumol was able to directly bind to the TOPK protein, suggesting that TOPK inactivation by xanthohumol is attributed to its ability to directly interact with TOPK. The findings of the present study identified TOPK as a direct target for xanthohumol to exert its anticancer activity, revealing novel insight into the mechanisms underlying the anticancer activity of xanthohumol.
CONFLICT OF INTEREST
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
All data generated or analyzed during this research has been included in this published study.
Supporting Information
| Filename | Description |
|---|---|
| ptr7799-sup-0001-Figures.docxWord 2007 document , 546.5 KB | Figure S1. The expression of TOPK in immortalized human lung fibroblast cell line MRC-5, lung cancer cell line A549, HCC827 and colorectal cancer cell line HCT116. Figure S2. Molecular docking of IX, DX and XD with TOPK. (A–C) IX, DX and XD bindings to the ATP-binding pocket of TOPK, respectively. TOPK protein is shown in green solid ribbon representation. IX, DX and XD are shown in ball-stick representation. (D–F) The ligand interactions of IX, DX and XD with TOPK, respectively. Key residues on TOPK are shown in ball-stick representation. Hydrogen and hydrophobic bonds are represented by the green and pink dashed lines, respectively. |
| ptr7799-sup-0002-WBimages.docxWord 2007 document , 777.7 KB | Data S1. Supporting information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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