Alpha 1-acid glycoprotein, alpha 2-HS glycoprotein, alpha 1-antitrypsin, and fragments thereof induce apoptosis in cancer cell lines

Abstract

This invention characterizes the selective apoptotic activity of specially prepared zinc charged alpha 1-acid glycoprotein, alpha 2-HS glycoprotein, and alpha 1-antitrypsin. These proteins cause apoptosis in cancer cells while leaving normal cells intact. In addition, active fragments of zinc charged alpha 1-acid glycoprotein and alpha 2-HS glycoprotein, whether manufactured from the modification of natural alpha 1-acid glycoprotein or alpha 2-HS glycoprotein, recombinantly, or synthetically, selectively induce apoptosis.

1 . A method of inducing apoptosis in cancer cells by administering alpha 1-acid glycoprotein to said cancer cells.  
     
     
         2 . The method of  claim 1  wherein said alpha 1-acid glycoprotein has been charged with zinc.  
     
     
         3 . A method of inducing apoptosis in cancer cells by administering alpha 2-HS glycoprotein to said cancer cells.  
     
     
         4 . The method of  claim 3  wherein said alpha 2-HS glycoprotein has been charged with zinc.  
     
     
         5 . A method of inducing apoptosis in cancer cells by administering alpha 1-antitrypsin to said cancer cells.  
     
     
         6 . The method of  claim 5  wherein said alpha 1-antitrypsin has been charged with zinc.  
     
     
         7 . A method of inducing apoptosis in cancer cells by administering a peptide fragment of alpha 1-acid glycoprotein to said cancer cells.  
     
     
         8 . The method of  claim 7  wherein said peptide fragment of alpha 1-acid glycoprotein has been charged with zinc.  
     
     
         9 . A method of inducing apoptosis in cancer cells by administering a peptide fragment of alpha 2-HS glycoprotein to said cancer cells.  
     
     
         10 . The method of  claim 9  wherein said peptide fragment of alpha 2-HS glycoprotein has been charged with zinc.  
     
     
         11 . A process for preparing zinc charged alpha 1-acid glycoprotein which is suitable for treatment on cancer cells comprising: 
 a. incubating said alpha 1-acid glycoprotein in solution with a chelating agent;    b. isolating naked alpha 1-acid glycoprotein from step a;    c. incubating said naked alpha 1-acid glycoprotein in solution with Zinc Acetate; and    d. isolating zinc charged alpha 1-acid glycoprotein from the solution in step c.    
     
     
         12 . A process for preparing zinc charged alpha 2-HS glycoprotein, which is suitable for treatment on cancer cells comprising: 
 a. incubating said alpha 2-HS glycoprotein in solution with a chelating agent;    b. isolating naked alpha 2-HS glycoprotein from step a;    c. incubating said naked alpha 2-HS glycoprotein in solution with Zinc Acetate; and    d. isolating zinc charged alpha 2-HS glycoprotein from the solution in step c.    
     
     
         13 . A process for preparing zinc charged alpha 1-antitrypsin, which is suitable for treatment on cancer cells comprising: 
 a. incubating said alpha 1-antitrypsin in solution with a chelating agent;    b. isolating naked alpha 1-antitrypsin from step a;    c. incubating said naked alpha 1-antitrypsin in solution with Zinc Acetate; and    d. isolating zinc charged alpha 1-antitrypsin from the solution in step c.    
     
     
         14 . A method of preparing a peptide fragment having apoptotic activity isolated from alpha 1-acid glycoprotein comprising the following steps: 
 a. incubating said alpha 1-acid glycoprotein in solution with a chelating agent;    b. isolating naked alpha 1-acid glycoprotein from step (a);    c. incubating said naked alpha 1-acid glycoprotein in solution with zinc;    d. isolating zinc charged alpha 1-acid glycoprotein from the solution created in step (c);    e. drying said zinc charged alpha 1-acid glycoprotein from step (d);    f. isolating, from step (e), peptide fragments which have apoptotic activity in cancer cells.    
     
     
         15 . A method of preparing a peptide fragment having apoptotic activity isolated from alpha 2-HS glycoprotein comprising the following steps: 
 a. incubating said alpha 2-HS glycoprotein in solution with a chelating agent;    b. isolating naked alpha 2-HS glycoprotein from step (a);    c. incubating said naked alpha 2-HS glycoprotein in solution with zinc;    d. isolating zinc charged alpha 2-HS glycoprotein from the solution created in step (c);    e. drying said zinc charged alpha 2-HS glycoprotein from step (d);    f. isolating, from step (e), peptide fragments which have apoptotic activity in cancer cells.    
     
     
         16 . A method of preparing a peptide fragment having apoptotic activity isolated from alpha 1-acid glycoprotein comprising the following steps: 
 a. incubating said alpha 1-acid glycoprotein in solution with a chelating agent;    b. isolating naked alpha 1-acid glycoprotein from step (a);    c. incubating said naked alpha 1-acid glycoprotein in solution with zinc;    d. isolating zinc charged alpha 1-acid glycoprotein from the solution created in step (c);    e. incubating the zinc charged alpha 1-acid glycoprotein from step (d) with papain;    f. isolating, from step (e), peptide fragments which have apoptotic activity in cancer cells.    
     
     
         17 . A method of preparing a peptide fragment having apoptotic activity isolated from alpha 2-HS glycoprotein comprising the following steps: 
 a. incubating said alpha 2-HS glycoprotein in solution with a chelating agent;    b. isolating naked alpha 2-HS glycoprotein from step (a);    c. incubating said naked alpha 2-HS glycoprotein in solution with zinc;    d. isolating zinc charged alpha 2-HS glycoprotein from the solution created in step (c);    e. incubating the zinc charged alpha 2-HS glycoprotein from step (d) with papain;    f. isolating, from step (e), peptide fragments which have apoptotic activity in cancer cells.