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Title 

Piperlongumine derivative, CG-06, inhibits STAT3 activity by direct binding to STAT3 and regulating the reactive oxygen species in DU145 prostate carcinoma cells

 

Piperlongumine derivative의 항암효과

Authors 

Young Hwan KimYae Jin YoonYu Jin LeeC H KimSangku LeeDong-Ho ChoungDong Cho HanByoung-Mog Kwon

Publisher 

Elsevier

Issue Date 

2018

Citation 

Bioorganic & Medicinal Chemistry Letters

Keywords 

ApoptosisPiperlongumineProstate cancerROSSTAT3

Abstract 

Piperlongumine (PL), isolated from Piper longum L., is receiving intense interest due to its selectively ability to kill cancer cells but not normal cells. We synthesized a number of analogues by replacing the cyclic amide of PL with aliphatic amides to explore structural diversity. Compound CG-06 had the strongest cytotoxic profile of this series, showing potent effects in human prostate cancer DU-145 cells, in which signal transducer and activator of transcription 3 (STAT3) is constitutively active. CG-06 inhibited STAT3 phosphorylation at tyrosine 705 in a dose- and time dependent manner in DU-145 cells and suppressed IL-6-induced STAT3 phosphorylation at Tyr-705 in DU-145 and LNCaP cell lines. CG-06 decreased the expression levels of STAT3 target genes, such as cyclin A, Bcl-2, and survivin. Notably, we used drug affinity responsive target stability (DARTS) to show that CG-06 binds directly to STAT3, and the reactive oxygen species (ROS) scavenger N-acetyl cysteine (NAC) rescued the CG-06-induced suppression p-STAT3. Our results suggest that CG-06 is a novel inhibitor of STAT3 and may be a useful lead molecule for the development of a therapeutic STAT3 inhibitor.

ISSN 

0960-894X

Link 

http://dx.doi.org/10.1016/j.bmcl.2018.05.025

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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