Investigations of DNA Alterations Induced by Doxorubicin and Analogs
Doxorubicin (DOX) is an anthracycline chemotherapeutic that has been used in the treatment of cancer since its discovery in the late 1960s. DOX’s mechanism of action is still unclear, but is thought to include the intercalation of DNA, halting transcription and inducing apoptosis. Although DOX has shown strong antitumor activity, its usage is limited due to a dose-dependent onset of cumulative and irreversible life-threatening cardiac damage. Consequently, the harmful side effects necessitate the need for the production of new, less harmful anthracycline chemotherapeutics with greater effectiveness for the treatment of cancer. Two analogs of DOX (GPX-150 and GPX-160) have been synthesized and determined to have antitumor activity against multiple cancer cell lines. This study seeks to investigate the mechanism by which these analogs display their activity, specifically probing for DNA modification by the alkaline COMET, Hoechst DNA-DNA crosslinking, and the K-SDS DNA-protein crosslinking assays. Each compound was tested for and found to have greater DNA-modifying abilities than DOX. These and related experimental results will be presented.
Kulm, Hannah and Pickering, Mikaela, "Investigations of DNA Alterations Induced by Doxorubicin and Analogs" (2016). 2016 Undergraduate Research and Scholarship Conference. Paper 77.