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Title 

2'-Hydroxycinnamaldehyde inhibits proliferation and induces apoptosis via signal transducer and activator of transcription 3 inactivation and reactive oxygen species generation

 

2’-Hydroxycinnamaldehyde는 STAT3와 ROS의 활성 조절을 통해 항암 효과

Authors 

Yae Jin YoonYoung Hwan KimYu Jin LeeJiyeon ChoiC H KimDong Cho HanByoung-Mog Kwon

Publisher 

Wiley

Issue Date 

2019

Citation 

Cancer Science

Keywords 

2-HydroxycinnamaldehydeROSSTAT3anticancerantioxidant

Abstract 

Inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling pathway is a novel therapeutic strategy to treat human cancers with constitutively active STAT3. During the screening of natural products to find STAT3 inhibitors, we identified 2'-hydroxycinnamaldehyde (HCA) as a STAT3 inhibitor, which was isolated from the stem bark of Cinnamomum cassia. In this study, we found that HCA inhibited constitutive and inducible STAT3 activation in STAT3-activated DU145 prostate cancer cells. HCA selectively inhibited the STAT3 activity by direct binding to STAT3, which was confirmed by biochemical methods, including a pull-down assay with biotin-conjugated HCA, a drug affinity responsive target stability (DARTS) experiment and a cellular thermal shift assay (CETSA). HCA inhibited STAT3 phosphorylation at the tyrosine 705 residue, dimer formation, and nuclear translocation in DU145 cells, which led to a downregulation of STAT3 target genes. The downregulation of cell cycle progression and antiapoptosis-related gene expression by HCA induced the accumulation of cells in the G0/G1 phase of the cell cycle and then induced apoptosis. We also found that reactive oxygen species (ROS) were involved in the HCA-induced inhibition of STAT3 activation and cell proliferation because the suppressed p-STAT3 level was rescued by glutathione or N-acetyl-L-cysteine treatment, which are general ROS inhibitors. These results suggest that HCA could be a potent anticancer agent targeting STAT3-activated tumor cells.

ISSN 

1347-9032

Link 

http://dx.doi.org/10.1111/cas.13852

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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