Abstract
Cancer stem cells (CSCs) are undifferentiated cells that give rise to tumor and resistance to chemotherapy. This study reports that phenylacetaldehyde (PAA), a flower flavor, inhibits formation on breast CSCs. PAA showed anti-proliferation and increased apoptosis of breast cancer. PAA also reduced tumor growth in an in vivo mice model. PAA reduced the CD44+/CD24- and ALDH1-expressing cells, mammosphere formation, and CSC marker genes. PAA preferentially induced reactive oxygen species (ROS) production and combined treatment with PAA and N-acetyl cysteine (NAC) decreased inhibition of mammosphere formation. PAA reduced phosphorylation of nuclear Stat3. PAA inhibited Stat3 signaling through de-phosphorylation of Stat3 and reduced secretory IL-6. Our results suggest that the PAA-induced ROS deregulated Stat3/IL-6 pathway and PAA may be a potential agent targeting breast cancer and CSCs.