Open AccessSuramin, screened from an approved drug library, inhibits HuR functions and attenuates malignant phenotype of oral cancer cells
Author(s) -
Kakuguchi Wataru,
Nomura Takao,
Kitamura Tetsuya,
Otsuguro Satoko,
Matsushita Kazuhiro,
Sakaitani Masahiro,
Maenaka Katsumi,
Tei Kanchu
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1877
Subject(s) - suramin , cancer cell , gene knockdown , cancer research , cyclin d1 , microbiology and biotechnology , cancer , biology , cyclin b1 , cell culture , cell growth , chemistry , pharmacology , cell cycle , biochemistry , in vitro , genetics , cyclin dependent kinase 1
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.