Induction of apoptosis in human lung cancer cells after wild-type p53 activation by methoxyestradiol

Abstract

2-methoxyestradiol (2-MeOE₂) treatment caused significant growth inhibition of H460 and A549 human lung cancer cell lines which contain wild-type p53. However, 2-MeOE₂ had a little effect on the p53 negative H358 and p53 mutated H322 cell lines. Western blot analysis indicated that 2-MeOE₂ treatment resulted in an eightfold increase in the endogenous wild-type p53 protein, while the level of the mutant p53 protein remained unchanged. TdT staining indicated that following 2-MeOE₂-mediated increases in wildtype p53 protein, cells bypass the G₁-S checkpoint of the cell cycle with 30 to 40% undergoing apoptosis. Introduction of anti-sense wt-p53 into wt-p53 cells abrogated the 2-MeOE₂ effect. A significant portion of lung cancer retains the wild-type p53 gene therefore, 2-MeOE₂ may have therapeutic application.