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Title 

MMPP attenuates non-small cell lung cancer growth by inhibiting the STAT3 DNA-binding activity via direct binding to the STAT3 DNA-binding domain

Authors 

D J SonJ ZhengY Y JungC J HwangH P LeeJ R WooS Y BaekY W HamM W KangM ShongG R KweonM J SongJ K JungS B HanBo Yeon KimD Y YoonB Y ChoiJ T Hong

Publisher 

Ivyspring International Publisher

Issue Date 

2017

Citation 

Theranostics

Keywords 

(E)-2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenolAnticancerDNA-binding domainNSCLCSTAT3

Abstract 

Rationale: Signal transducer and activator of transcription-3 (STAT3) plays a pivotal role in cancer biology. Many small-molecule inhibitors that target STAT3 have been developed as potential anticancer drugs. While designing small-molecule inhibitors that target the SH2 domain of STAT3 remains the leading focus for drug discovery, there has been a growing interest in targeting the DNA-binding domain (DBD) of the protein. Methods: We demonstrated the potential antitumor activity of a novel, small-molecule (E)-2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol (MMPP) that directly binds to the DBD of STAT3, in patient-derived non-small cell lung cancer (NSCLC) xenograft model as well as in NCI-H460 cell xenograft model in nude mice. Results: MMPP effectively inhibited the phosphorylation of STAT3 and its DNA binding activity in vitro and in vivo. It induced G1-phase cell cycle arrest and apoptosis through the regulation of cell cycle- and apoptosis-regulating genes by directly binding to the hydroxyl residue of threonine 456 in the DBD of STAT3. Furthermore, MMPP showed a similar or better antitumor activity than that of docetaxel or cisplatin. Conclusion: MMPP is suggested to be a potential candidate for further development as an anticancer drug that targets the DBD of STAT3

ISSN 

1838-7640

Link 

http://dx.doi.org/10.7150/thno.18630

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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