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.