Molecular Mechanism of an Apoptosis Indusing Estrogen Metabolite 2 Methoxyestradiol

Lung cancer is the second most common of cancer in the United States, and it is the most lethal, accounting for approximately 28% of cancer deaths. This mortality rate is greater than that attributable to colorectal, breast, pancreatic and prostate cancer combined. The Commonwealth of Kentucky, in particular, has the highest incidence of lung cancer in the country. Moreover, because of the large population of smoking teenagers in the United States which is about the same number as that of smoking adults, lung cancer will likely remain as a major health problem in the future. However, systemic treatments for lung cancer with standard chemotherapy agents are still relatively ineffective and, therefore, novel approaches are needed to improve the odds for patients at risk. A natural product called 2-methoxyestradiol present in human urine has been shown to selectively kill lung cancer cells but not human normal lung cells. Therefore, the project proposed here is focused on molecular-level-understanding of how 2-methoxyestradiol selectively kills lung cancer cells compared with human normal lung cells. Ultimately, a better understanding of how 2- methoxyestradiol works will have direct translational potential in the development of better regimens for its use in treating lung cancers.