Fig. 7
From: DNA damage and apoptosis induced by a potent orally podophyllotoxin derivative in breast cancer
Mechanism of XWL-1-48 inhibits growth of breast cancer cells. XWL-1-48, a novel orally topoisomeraseII inhibitor, exerts potent in vitro and in vivo anti-tumor activity against breast cancer. Treatment with XWL-1-48 significantly inhibited TopoII activity, triggered DNA damage response, activated ATM/p53/p21 pathways, arrested cell cycle at S phase, and induced mitochondria-mediated apoptosis. Meanwhile, XWL-1-48 strongly blocked PI3K/Akt/Mdm2 pathway, prompted degradation of Mdm2, and suppressed breast cancer cell survival