Acridine-based agents with topoisomerase II activity inhibit pancreatic cancer cell proliferation and induce apoptosis

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.