Inhibition of Cellular Growth and DNA Replication by Anthracycline Analogs

Faculty Mentor Information

Phil Moon, Dr. Ken Cornell Ph.D., and Dr. Don Warner Ph.D.

Presentation Date

7-2016

Abstract

Doxorubicin (DOX) is a leading drug used to treat soft tissue sarcomas (STS), but has shown a limited effectiveness because of serious drug-induced cardiotoxicity. Two new DOX derivatives, GPX-150 and GPX-160, have been developed to overcome this toxicity. The current study involves determining the in vitro anti-proliferative effects of these compounds against human cancer and normal cells. Based on the in vitro cell viability data, the GPX-series compounds show promise as anti-cancer agents. One of the known DOX mechanisms of action is interference with DNA replication through inhibition of DNA topoisomerase II and gyrase enzymes. To examine whether the GPX-series compounds also inhibit these enzymes, topoisomerase and gyrase activity assays were performed and analyzed by gel electrophoresis. The results indicate that the GPX-series compounds also affect topoisomerase and gyrase activity at low micromolar concentrations.

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Poster #Th17

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Inhibition of Cellular Growth and DNA Replication by Anthracycline Analogs

Doxorubicin (DOX) is a leading drug used to treat soft tissue sarcomas (STS), but has shown a limited effectiveness because of serious drug-induced cardiotoxicity. Two new DOX derivatives, GPX-150 and GPX-160, have been developed to overcome this toxicity. The current study involves determining the in vitro anti-proliferative effects of these compounds against human cancer and normal cells. Based on the in vitro cell viability data, the GPX-series compounds show promise as anti-cancer agents. One of the known DOX mechanisms of action is interference with DNA replication through inhibition of DNA topoisomerase II and gyrase enzymes. To examine whether the GPX-series compounds also inhibit these enzymes, topoisomerase and gyrase activity assays were performed and analyzed by gel electrophoresis. The results indicate that the GPX-series compounds also affect topoisomerase and gyrase activity at low micromolar concentrations.