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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Dental Medicine / Faculty of Dental Medicine >
Peer-reviewed Journal Articles, etc >
Suramin, screened from an approved drug library, inhibits HuR functions and attenuates malignant phenotype of oral cancer cells
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| Title: | Suramin, screened from an approved drug library, inhibits HuR functions and attenuates malignant phenotype of oral cancer cells |
| Authors: | Kakuguchi, Wataru Browse this author →KAKEN DB | | Nomura, Takao Browse this author | | Kitamura, Tetsuya Browse this author →KAKEN DB | | Otsuguro, Satoko Browse this author | | Matsushita, Kazuhiro Browse this author →KAKEN DB | | Sakaitani, Masahiro Browse this author | | Maenaka, Katsumi Browse this author →KAKEN DB | | Tei, Kanchu Browse this author →KAKEN DB |
| Keywords: | AU-rich elements | | drug repositioning | | HuR | | screening | | suramin |
| Issue Date: | Dec-2018 |
| Publisher: | John Wiley & Sons |
| Journal Title: | Cancer medicine |
| Volume: | 7 |
| Issue: | 12 |
| Start Page: | 6269 |
| End Page: | 6280 |
| Publisher DOI: | 10.1002/cam4.1877 |
| Abstract: | AU-rich elements (ARE) exist in the 3 '-untranslated regions of the mRNA transcribed from cell growth-related genes such as proto-oncogenes, cyclin-related genes, and growth factors. HuR binds and stabilizes ARE-mRNA. HuR is expressed abundantly in cancer cells and related malignant phenotypes. HuR knockdown attenuates the malignant phenotype of oral cancer cells. In this study, we screened 1570 compounds in the approved drug library by differential scanning fluorimetry (DSF) to discover a HuR-targeted compound. Firstly, 55 compounds were selected by DSF. Then, 8 compounds that showed a shift in the melting temperature value in a concentration-dependent manner were selected by DSF. Of them, suramin, an anti-trypanosomal drug, binds to HuR, exhibiting fast-on and fast-off kinetic behavior on surface plasmon resonance (SPR). We confirmed that suramin significantly decreased mRNA and protein expression of cyclin A2 and cyclin B1. The cyclin A2 and cyclin B1 mRNAs were destabilized by suramin. Furthermore, the motile and invasive activities of a tongue carcinoma cell line treated with suramin were markedly lower than those of control cells. The above findings suggest that suramin binds to HuR and inhibits its function. We also showed that the anticancer effects of suramin were caused by the inhibition of HuR function, indicating its potential as a novel therapeutic agent in the treatment of oral cancer. Our results suggest that suramin, via its different mechanism, may effectively suppress progressive oral cancer that cannot be controlled using other anticancer agents. |
| Rights: | Suramin, screened from an approved drug library, inhibits HuR functions and attenuates malignant phenotype of oral cancer cells. Wataru Kakuguchi, Takao Nomura, Tetsuya Kitamura, Satoko Otsuguro, Kazuhiro Matsushita, Masahiro Sakaitani, Katsumi Maenaka and Kanchu TeiAuthor. Cancer medicine 7(12). Copyright The Authors. | | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/72707 |
| Appears in Collections: | 歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 格口 渉
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