2-Methoxyestradiol-induced apoptosis in cancer cells

Abstract

The present invention details methods for the treatment of cancer. In particular, it concerns the induction of apoptosis of cancer cells following treatment with methoxyestradiol. 2-methoxyestradiol (2-MeOE 2 ) increase wild-type p53 levels in a human non-small lung cancer cell lines associated with accumulation of cyclin dependent kinase inhibitor p21WAF1/CIP1. Significant apoptotic cell death occurred after the drug treatment. Thus, 2-MeOE 2 facilitates induction of p53-mediated apoptosis.

What is claimed is:  
     
         1 . A method for increasing the level of p53 in a cell having a functional p53 therein, comprising the step of contacting said cell with an amount of 2-methoxyestradiol sufficient to increase the level of p53 in said cell.  
     
     
         2 . The method of  claim 1 , wherein said p53 is an endogenous protein.  
     
     
         3 . The method of  claim 1 , wherein said p53 is an exogenous protein.  
     
     
         4 . The method of  claim 2 , wherein said cell further contains an exogenous p53 protein.  
     
     
         5 . The method of  claim 1 , wherein said cell is an endothelial cell.  
     
     
         6 . The method of  claim 1 , wherein said cell is a tumor cell.  
     
     
         7 . The method of  claim 6 , wherein said cell is a lung tumor cell.  
     
     
         8 . The method of  claim 7 , wherein said cell is a non-small cell lung carcinoma cell.  
     
     
         9 . A method for inducing apoptosis in a cell having a transcriptionally active p53 gene therein comprising the step of contacting said cell with an amount of 2-methoxyestradiol sufficient to induce apoptosis in said cell.  
     
     
         10 . The method of  claim 9 , wherein said p53 gene is an endogenous gene.  
     
     
         11 . The method of  claim 9 , wherein said p53 gene is an exogenous gene.  
     
     
         12 . The method of  claim 11 , wherein said cell further contains a transcriptionally active exogenous p53 gene.  
     
     
         13 . The method of  claim 9 , wherein said cell is an endothelial cell.  
     
     
         14 . The method of  claim 9 , wherein said cell is a tumor cell.  
     
     
         15 . The method of  claim 14 , wherein said cell is a lung tumor cell.  
     
     
         16 . The method of  claim 15 , wherein said cell is a non-small cell lung carcinoma cell.  
     
     
         17 . A method for treating cancer in a patient comprising the steps of: 
 (a) determining the p53 status of a tumor cell in said patient;    (b) contacting said tumor cell with an amount of 2-methoxyestradiol sufficient to induce apoptosis in said cell.    
     
     
         18 . The method of  claim 17 , wherein said p53 status of said tumor cell contains a functional p53.  
     
     
         19 . The method of  claim 17 , wherein said p53 status of said tumor cell lacks a functional p53 protein and said method further comprises the transfer of a wild-type p53 gene into said tumor cell.  
     
     
         20 . The method of  claim 19 , wherein said transfer comprises contacting said tumor cell with an adenovirus containing said wild-type p53 gene.  
     
     
         21 . The method of  claim 20 , wherein said adenovirus is replication defective.  
     
     
         22 . The method of  claim 21 , wherein said adenovirus is lacking at least a portion of the E1 region.  
     
     
         23 . The method of  claim 17 , wherein said cell is a lung tumor cell.  
     
     
         24 . The method of  claim 23 , wherein said cell is a non-small cell lung carcinoma cell.  
     
     
         25 . The method of  claim 17 , wherein said contacting comprises intravenous administration.  
     
     
         26 . The method of  claim 17 , wherein said contacting comprises intratumoral administration.  
     
     
         27 . A kit comprising: 
 (a) 2-methoxyestradiol; and    (b) an expression vector encoding a wild-type p53 gene under the control of a promoter active in eukaryotic cells,    both said 2-methoxyestradiol and said expression vector provided in suitable container means.    
     
     
         28 . A kit comprising: 
 (a) 2-methoxyestradiol; and    (b) an antibody that binds immunologically to p53,    both said 2-methoxyestradiol and said antibody provided in suitable container means.    
     
     
         29 . A kit comprising: 
 (a) 2-methoxyestradiol; and    (b) a nucleic acid that binds hybridizes specifically to p53,    both said 2-methoxyestradiol and said nucleic acid provided in suitable container means.