Developing chemotherapeutics with enhanced selectivity is a major goal in cancer drug design. With this objective in mind, we synthesized novel anti-cancer agents using a pro-drug strategy. The agents developed using this method, are activated by oxidative stress, a hallmark of many cancer cells. These new agents have been shown to be selective, with over 200-fold differences in the cytotoxicity in different cancer cell lines. We focused on renal and leukemia cancer lines, to identify the resulting gene expression. We have investigated genes in three categories: oncogenes, antioxidant defense and DNA repair. By correlating potency with normalized gene expression in 111 transcripts, thirteen genes have been identified (r>0.5). The antioxidant transcript SOD1 affected potency by decreasing the drug's cytotoxicity. Based on this data and known scientific literature, we propose the ROS type that activates oxidatively-activated agents intracellularly. We are now carrying out experiments to prove the type of reactive oxygen species responsible for activation.

Transcriptome profiling of an oxidatively-activated agent reveals the reactive oxygen species responsible for activation

245th National Meeting (2013)

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