Author(s): Mukhopadhyay T, Roth JA
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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.
This article was published in Oncogene
and referenced in Journal of Cancer Science & Therapy