Study of a Molecular Promoter for Enhancing Cisplatin Cancer Chemotherapy

Abstract

Cisplatin is one of the most widely used chemotherapeutic anti-cancer drugs due to its ability to effectively damage DNA and cause cell death. Despite this, cisplatin still suffers from two main drawbacks: toxicity and drug resistance. Many cisplatin-like compounds have been synthesized via traditional methods of drug design but very few have been able to enter clinical trials or even be approved for clinical use. The reason why so many compounds have been rejected is that their reaction mechanisms are rarely understood. By observing and studying the reaction mechanisms of a drug at the molecular level, the reaction can be optimized to enhance its therapeutic effects. The powerful technique of time-resolved pump-probe femtosecond laser spectroscopy was performed by Lu et al. to reveal the extremely high reactivity of cisplatin with weakly-bound electrons, thus providing a deeper understanding of this drug’s therapeutic effects. Taking advantage of this reaction mechanism, a molecular promoter can be identified to amplify the therapeutic efficacy of cisplatin by combination in a synergistic manner. Through cell survival rate measurements, fluorescence microscopic studies to view cell death, cell cycle analysis and DNA fragmentation measurements via flow cytometry, as well as absorption spectroscopic studies, the synergistic effects between cisplatin and a new molecular promoter (PM2A) were measured. This new chemotherapeutic regimen, which was designed based on the electron-transfer reaction mechanism of cisplatin, can be used to decrease the required doses of cisplatin used in the clinic (to effectively reduce its toxic side effects), to circumvent the drug resistance and to improve targeting to cancer cells.