A Dual Topoisomerase Inhibitor, TAS‐103, Induces Apoptosis in Human Cancer Cells

TAS‐103 (6‐[[2‐(dimethylamino)ethyl]amino]‐3‐hydroxy‐7H‐indeno[2,1‐c]quinolin‐7‐one dihydrochloride), a dual topoisomerase (topo) inhibitor, was developed as an anticancer agent by targeting topo I and topo II and has previously been shown to be effective against lung tumors. In this study, we investigated the cytotoxic activity of TAS‐103 in various human cancer cell lines (including gastric, colon, squamous, lung, and breast cancer cells) and the induction of apoptosis by TAS‐103. We next established stable transfectants of Bcl‐2 in the gastric cancer cell line AZ521 and found that Bcl‐2 blocked TAS‐103‐induced apoptosis. In addition, we demonstrated that the activities of ICE‐like and CPP32‐like proteases are involved in the signal transduction pathway of TAS‐103‐induced apoptosis. In summary, TAS‐103 is a novel type of anticancer agent with a unique mechanism and could be useful as a lead compound for development of new drugs.