Yatein-induced DNA damage of breast cancer cells by interfering with DNA topoisomerase IIα

DNA topoisomerase IIα (TOP2A) plays a key role in resolving DNA topological stress during replication, transcription, and chromosome segregation. Yatein, a biogenic precursor of deoxypodophyllotoxin possesses antitumor effects. Herein, we explored its antitumor effect in breast cancer. Yatein significantly inhibited the proliferation of breast cancer cells by MTT, colony formation, EdU assay, and cell cycle analysis. Moreover, yatein suppressed the stemness of cancer cells, causing inhibition of migration and epithelial-mesenchymal transition. Mechanism study revealed that yatein inhibited TOP2A activity and stabilized TOP2A-DNA cleavage complexes, caused DNA damage and apoptosis, suggesting its potential in the treatment of breast cancer.