Acridine-Based Agents with Topoisomerase II Activity Inhibit Pancreatic Cancer Cell Proliferation and Induce Apoptosis

Abstract

A series of substituted 9-aminoacridines is evaluated for antiproliferative activity toward pancreatic cancer cells. The results indicate that the compounds inhibit cell proliferation by inducing a G1-S phase arrest. A model is also developed that explains the molecular basis to inhibition through a DNA “threading” mechanism. We conclude that the drug–DNA complex formed blocks topoisomerase II binding and activity leading to catalytic inhibition of the enzyme and the induction of apoptosis and programmed cell death