%0 Journal Article
%T 2¡ä©\Hydroxycinnamaldehyde inhibits proliferation and induces apoptosis via signal transducer and activator of transcription 3 inactivation and reactive oxygen species generation
%A Byoung©\Mog Kwon
%A Cheol©\Hee Kim
%A Dong Cho Han
%A Jiyeon Choi
%A Yae Jin Yoon
%A Young©\Hwan Kim
%A Yu©\Jin Lee
%J Archive of "Cancer Science".
%D 2019
%R 10.1111/cas.13852
%X 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¡ä©\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
%K 2©\Hydroxycinnamaldehyde
%K anticancer
%K antioxidant
%K ROS
%K STAT3
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317917/