"Selectively Killing Cancers Through Catalytically Destroying their Anti-Oxidative Defenses"
Jie Song, Ph.D.
Department of Chemistry
Cancer remains a leading killer: 14 million new cases and 8.2 million cancer deaths worldwide were recorded in the year 2012 while the incidence and mortality are estimated to rise to 21 million and 13 million by 2030, respectively (Cancer Statistics, NCI website). The fact that cancer variants have evolved into new and intractable types or subtypes, which exhibit inherent or acquired resistance to current clinically-used chemotherapeutics, imposes a challenge in cancer treatments. Extensive efforts have been devoted to the development of new anti-cancer agents including both chemical, immunological, and biologic therapeutics, however, the success rate remains very low. Developing new anti-cancer therapeutics, ideally with novel mechanisms of action is extremely challenging. In this talk, I will present our recent discovery that a nanoscale zwitterionic molecule, VPOA-6, exhibits remarkable selectivity in killing cancer cells while sparing normal cells in vitro. Our in vivo data demonstrate this agent markedly inhibits human tumor growth in mouse models. Mechanistic studies reveal that VPOA-6 dramatically alters the cancer redox balance by devastating its antioxidative capacity, leading to a ROS surge and cell apoptosis. These data further lead us to determine the relationship between the structural and other properties of VPOA-6 and its cancer-killing effect as well as its efficacy in tumor inhibition.