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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)

Submitter: 格口 渉

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