Human Breast Cancer DNA Synthesome Can Serve as a Novel In Vitro Model System for Studying the Mechanism of Action of Anticancer Drugs

摘要

Gemcitabine (dFdC) and cytarabine (araC) are both analogs of deoxycytidine. In this report, we compared the effects of dFdC and araC on in vitro DNA synthesis mediated by the DNA synthesome with the effects of these drug on intact MCF7 cell DNA synthesis. We also examined the effects of dFdC and AraC on their associated target protein, DNA polymerases alpha, and delta. Our results showed that (1) dFdC is a more potent inhibitor of intact cell DNA synthesis and in vitro SV4O DNA replication than araC; (2) the decrease in the synthetic activity of synthesome-mediated in vitro SV4O origin dependent DNA synthesis by dFdCTP and araCTP correlates with the inhibition of DNA polymerase a activity; and (3) the MCF7 cell DNA synthesome can serve as a unique and relevant model to study the mechanism of action of anticancer drugs that directly affect DNA synthesis.