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https://ir.csmu.edu.tw:8080/ir/handle/310902500/23683
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Title: | Adenine Inhibits the Invasive Potential of DLD-1 Human Colorectal Cancer Cell via the AMPK/FAK Axis |
Authors: | Huang, CW;Lin, YC;Hung, CH;Chen, HM;Lin, JT;Wang, CJ;Kao, SH |
Keywords: | adenine;colorectal cancer cell;invasion;AMP-activated protein kinase;focal adhesion kinase |
Date: | 2021 |
Issue Date: | 2022-08-05T09:41:13Z (UTC)
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Publisher: | MDPI |
Abstract: | Tumor metastasis is a major cause of death of patients with colorectal cancer (CRC). Our previous findings show that adenine has antiproliferation activity against tumor cells. However, whether adenine reduces the invasiveness of DLD-1 and SW480 CRC cells has not been thoroughly explored. In this study, we aimed to explore the effects of adenine on the invasion potential of DLD-1 cells. Our findings showed that adenine at concentrations of <= 200 mu M did not influence the cell viability of DLD-1 and SW480 CRC cells. By contrast, adenine reduced the migratory potential of the CRC cells. Moreover, it decreased the invasion capacity of the CRC cells in a dose-dependent manner. We further observed that adenine downregulated the protein levels of tissue plasminogen activator, matrix metalloproteinase-9, Snail, TWIST, and vimentin, but upregulated the tissue inhibitor of metalloproteinase-1 expression in DLD-1 cells. Adenine decreased the integrin alpha V level and reduced the activation of integrin-associated signaling components, including focal adhesion kinase (FAK), paxillin, and Src in DLD-1 cells. Further observations showed that adenine induced AMP-activated protein kinase (AMPK) activation and inhibited mTOR phosphorylation in DLD-1 cells. The knockdown of AMPK restored the reduced integrin alpha V level and FAK/paxillin/Src signaling inhibited by adenine in DLD-1 cells. Collectively, these findings reveal that adenine reduces the invasion potential of DLD-1 cells through the AMPK/integrin/FAK axis, suggesting that adenine may have anti-metastatic potential in CRC cells. |
URI: | http://dx.doi.org/10.3390/ph14090860 https://www.webofscience.com/wos/woscc/full-record/WOS:000701928800001 https://ir.csmu.edu.tw:8080/handle/310902500/23683 |
Relation: | PHARMACEUTICALS ,2021,v14,issue 9 |
Appears in Collections: | [中山醫學大學研究成果] 期刊論文
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