Selenium-containing coordinating assemblies with selective anti-cancer activity: the control of reactive oxygen species

Abstract

Reactive oxygen species (ROS) attract increasing interests due to the function of "double-edged sword" in physiological condition. In low concentration, ROS can benefit the growth of normal cells; however, in high concentration, they will induce cell apoptosis. Selenium is an essential trace element of human beings that can regulate the concentration of ROS. Previous work demonstrated the selective anti-cancer activity of coordinating assemblies consisting of selenium-containing amphiphile (EGSe) and cisplatin, but the structure and mechanism remain unclear. We synthesized another selenium-containing amphiphile-trimethyl-EGSe (EGSe-tMe) which has similar structure with EGSe but forms weaker interaction with platinum-containing compounds. Then, we prepared new coordinating assemblies composed of two types of selenium-containing amphiphiles and two types of platinum-containing compounds (cisplatin, platinum dichloride), in order to study the coordinating interaction between selenium and platinum. Additionally, we studied the mechanism of their selective anti-cancer activity by testing the ability of regulating ROS concentration in cancer cells and normal cells. We found that EGSe could coordinate with both cisplatin and platinum dichloride, resulting in the formation of coordinating assemblies with selective anti-cancer activity. However, coordinating assemblies consisting of EGSe-tMe and platinum-containing compounds showed little selectivity. These results indicate the important role of tight interaction between selenium and platinum played in the selective anti-cancer activity. The anti-cancer activity comes from their function of regulating the concentration of ROS in cells. Selenium-containing coordinating assemblies can raise higher concentration of ROS in cancer cells than in normal cells, thus causing selective toxicity to cancer cells. In further study, we proposed the mechanism of ROS production by selenium-containing coordinating assemblies. The coordinating assemblies can induce ROS production with the proof of electron spin resonance (ESR) measurement. We hope that this work can not only broaden the applications of selenium- containing coordinating assemblies in the field of cancer treatment, but also provide a new route for developing selective anti-cancer drugs.