Planta Med 2010; 76 - P247
DOI: 10.1055/s-0030-1264545

Taiwanin A inhibits MCF-7 cancer cell activity through induction of oxidative stress, upregulation of DNA damage checkpoint kinases, and activation of p53 and FasL/Fas signaling pathways

L Shyur 1, S Lee 1, S Chang 2, C Lo 1, Y Kuo 3, S Wang 4
  • 1Academia Sinica, Agricultural Biotechnology Research Center, No 128, Sec 2, Academia Road, Nankang, 115 Taipei, Taiwan
  • 2National Taiwan University, School of Forestry and Resource Conservation and Department of Chemistry, National Taiwan University, 106 Taipei, Taiwan
  • 3Chinese Medical University, Graduate Institute of Pharmaceutical Chemistry, Chinese Medical University, 404 Taichung, Taiwan
  • 4National Chung-Hsing University, Department of Forestry, Department of Forestry, National Chung-Hsing University, 402 Taichung, Taiwan

This study investigates the anti-MCF-7 breast cancer cell effects and the underlying pharmacological activity and mechanism of taiwanin A, a major lignan isolated from Taiwania cryptomerioides. Our results show that taiwanin A time-dependently induced reactive oxygen species level and DNA damage in MCF-7 cells, which were likely activated ATM and Chk. Taiwanin A could also up-regulate p53, phosphorylated p53, p21Cip1, and p27Kip1 and down-regulate the G2/M checkpoint Cdk1-cyclin A/B, leading to induction of G2/M cell-cycle arrest in MCF-7 cells. Blockade of p53 gene expression by siRNA further demonstrated that the cell-cycle arrest induced by taiwanin A was p53-dependent. The FasL/Fas-mediated apoptotic signaling cascade was involved in taiwanin A-induced apoptosis via activation of caspases-10 and -7 (but not caspase-8), and proteolytic cleavage of PARP. In contrast, mitochondria-initiated apoptotic pathway was not involved. This is the first report to delineate novel mechanism of the action of taiwanin A against MCF-7 cells, suggesting this lignan may have value for development as an anti-breast cancer agent.