Cytotoxic factors for modulating cell death

Abstract

Cytotoxic factors having use in modulating cell death, and their use in methods of treating necrosis or apoptosis-related conditions are disclosed. The invention also relates to methods for identifying active agents useful in treating conditions related to cell death. The present inventors have found that different pathogens produce different cytotoxic factor(s) having anticancer activity. The substantially pure cytotoxic factors can be used in a method of treating an infectious disease or a cancer.

1 . A substantially pure protein, that is a mutant and/or truncation of azurin, and increases cell death of cancer cells.  
     
     
         2 . The substantially pure protein of  claim 1 , wherein the mutant is a genetically altered form of azurin.  
     
     
         3 . The substantially pure protein of  claim 1 , which increases apoptosis in cancer cells.  
     
     
         4 . The substantially pure protein of  claim 1 , wherein the cancer cells are selected from the group consisting of melanoma cells, leukemia cells, breast cancer cells, ovarian cancer cells, lung cancer cells, mesenchymal cancer cells, colon cancer cells, and aerodigestive tract cancer cells.  
     
     
         5 . The substantially pure protein of  claim 1 , which is in a pharmaceutically acceptable carrier.  
     
     
         6 . The substantially pure protein of  claim 5 , wherein the pharmaceutically acceptable carrier is suitable for intravenous administration.  
     
     
         7 . The substantially pure protein of  claim 1 , which has low antigenicity.  
     
     
         8 . The substantially pure protein of  claim 1 , wherein the azurin is from  Pseudomonas aeruginosa.    
     
     
         9 . A substantially pure protein, that is a mutant and/or truncation of cytochrome c 551 , and increases cell death of cancer cells.  
     
     
         10 . The substantially pure protein of  claim 9 , wherein the mutant is a genetically altered form of cytochrome c 551 .  
     
     
         11 . The substantially pure protein of  claim 9 , which increases apoptosis in cancer cells.  
     
     
         12 . The substantially pure protein of  claim 9 , wherein the cancer cells are selected from the group consisting of melanoma cells, leukemia cells, breast cancer cells, ovarian cancer cells, lung cancer cells, mesenchymal cancer cells, colon cancer cells, and aerodigestive tract cancer cells.  
     
     
         13 . The substantially pure protein of  claim 9 , which is in a pharmaceutically acceptable carrier.  
     
     
         14 . The substantially pure protein of  claim 13 , wherein the pharmaceutically acceptable carrier is suitable for intravenous administration.  
     
     
         15 . The substantially pure protein of  claim 9 , which has low antigenicity.  
     
     
         16 . The substantially pure protein of  claim 9 , wherein the cytochrome c 551  is from  Pseudomonas aeruginosa.    
     
     
         17 . A therapeutic composition, comprising one or more protein selected from the group consisting of azurin, a mutant and/or truncation of azurin, cytochrome c 551 , and a mutant and/or truncation of cytochrome c 551 , in a pharmaceutically acceptable carrier.  
     
     
         18 . The therapeutic composition of  claim 17 , wherein the pharmaceutically acceptable carrier is suitable for intravenous administration.  
     
     
         19 . The therapeutic composition of  claim 17 , which has low antigenicity.  
     
     
         20 . The therapeutic composition of  claim 17 , wherein the azurin is from  Pseudomonas aeruginosa.    
     
     
         21 . The therapeutic composition of  claim 17 , wherein the cytochrome c 551  is from  Pseudomonas aeruginosa.