Superinduction of wild-type p53 protein after 2-methoxyestradiol treatment of Ad5p53-transduced cells induces tumor cell apoptosis.
Because 2-methoxyestradiol (2-MeOE2) induces and stabilizes wild-type p53 protein (wt p53) in human lung cancer cell lines posttranscriptionally, we sought to study its effects on Ad5p53-transduced lung cancer cell lines at a low multiplicity of infection (1 MOI). Treating these cells with 2-MeOE2 resulted in superinduction of wt p53 protein expression followed by apoptosis, as shown by terminal deoxynucleotidyl transferase (TdT) staining, and upregulation of wt p53 expression, as shown by Western blot analysis. When transduced with Ad5p53 alone at 1 MOI, the cell lines grew rapidly. Moreover, adenoviral-vector-mediated p53 gene transfer followed by 2-MeOE2 treatment caused 80% growth inhibition in the cell lines regardless of their p53 status. Thus, p53 superinduction and apoptosis after 2-MeOE2 treatment in Ad5p53-transduced cells appears to be a unique strategy with significant implications for cancer gene therapy.
Department of Thoracic and Cardiovascular Surgery, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
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Mukhopadhyay
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Roth
D000077584:2-Methoxyestradiol; D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
D016159:Tumor Suppressor Protein p53; D004958:Estradiol; D000077584:2-Methoxyestradiol