Lindsay E. Calderon
In the United States one in eight women will be afflicted with breast cancer. Triple negative breast cancers account for 15% of these diagnoses and are significantly more aggressive than other subtypes, as well as, being difficult to treat. Current platinum drugs on the market, including cisplatin and carboplatin, have been shown to effectively improve patient prognosis, however, they cause numerous debilitating side effects. Subsequently, we have synthesized a new analog of carboplatin, “Platinum-Mal-LHRH”, to selectively target breast cancer cells overexpressing the LHRH receptor
Initial in-vitro results showed that Platinum-Mal-LHRH has a higher potency towards 4T1 (stage IV) breast cancer cells compared to carboplatin. Cell viability was analyzed by an MTT assay, resulting in significant, (p>0.01), reduction in viable cancer cells treated with Platinum-Mal-LHRH compared to carboplatin. Drug uptake was also evaluated by ICP-MS in which Platinum-Mal-LHRH displayed a 20-fold increase in cellular uptake compared to carboplatin. We also found that Platinum-Mal-LHRH selectively targets 4T1 breast cancer cells as there was a significant, (p>0.0001), decrease in 4T1 cell viability compared to normal mammary cells. To verify increased apoptosis, flow cytometry was used to compare the cell death of 4T1 treated with Pt-Mal-LHRH versus those treated with carboplatin. In-vivo tumor assessment was conducted and there was a significant decrease in tumor growth with Pt-Mal-LHRH treatment. Our data indicates that Platinum-LHRH is potentially a more potent and selective chemotherapeutic agent than other platinum based drugs currently on the market, such as carboplatin. Future directions include DNA analysis for adduct formation and quantification.