Induction of apoptosis in human lung cancer cells after wild-type p53 activation by methoxyestradiol.
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.
Mukhopadhyay
T
T
Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Roth
J A
JA
D000077584:2-Methoxyestradiol; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015152:Blotting, Northern; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016158:Genes, p53 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D004958:Estradiol; D000077584:2-Methoxyestradiol