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

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 the rmal 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 i nduced 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 glutathion e 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.
Source: Cancer Science - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research