Spalax fibroblast-derived anti-cancer agents

Abstract

A conditioned cell culture medium of cells derived from Spalax or naked mole rat ( Heterocephalus glaber ) and methods for preparing it are provided. Pharmaceutical compositions comprising the conditioned cell culture medium and its use in the treatment of cancer as well as methods for identifying anti-cancer agents are also provided.

1 . A conditioned cell culture medium of cells derived from  Spalax  or naked mole rat ( Heterocephalus glaber ), or a biologically active fraction thereof. 
     
     
         2 . The conditioned cell culture medium according to  claim 1 , wherein said cells are derived from  Spalax ehrenbergi  ( Nannospalax ). 
     
     
         3 . The conditioned cell culture medium according to  claim 1 , wherein said cells are skin or lung fibroblasts. 
     
     
         4 . The conditioned cell culture medium according to  claim 3 , wherein said fibroblasts are primary cells. 
     
     
         5 . A method for identifying an anti-cancer agent, comprising:
 a. obtaining a conditioned cell culture medium of cells according to any one of  claims 1  to  4 ;   b. fractionating said conditioned cell culture medium, thereby obtaining fractions;   c. contacting cancer cells and normal cells with said fractions of (b), and identifying active fractions that kill or inhibit the proliferation of cancer cells but have no or little effect on proliferation of normal cells; and   d. collecting said active fractions of (c) and optionally repeating step (c) until an anti-cancer agent is identified.   
     
     
         6 . The method according to  claim 5 , wherein said cancer and normal cells are human cells. 
     
     
         7 . The method according to  claim 6 , wherein said cancer are epithelial cells and said normal cells are mesenchymal cells. 
     
     
         8 . A method for producing a conditioned cell culture medium of cells derived from  Spalax  or naked mole rat ( Heterocephalus glaber ), comprising:
 a. obtaining  Spalax  or naked mole rat cells;   b. culturing said  Spalax  or naked mole rat cells in a growth medium. thereby producing a  Spalax  or naked mole rat cell-conditioned composition; and   c. collecting said  Spalax  or naked mole rat cell-conditioned composition.   
     
     
         9 . An active agent selected from: (i) a conditioned cell culture medium of cells derived from  Spalax  or naked mole rat ( Heterocephalus glaber ); (ii) a biologically active fraction of (i); or (iii) a pharmaceutical composition comprising (i) or (ii) and a pharmaceutically active carrier, excipient or diluent. 
     
     
         10 . A method for treatment of cancer or inhibiting cancer metastasis in a subject diagnosed with cancer, said method comprising administering to said subject an effective amount of the active agent according to  claim 9 . 
     
     
         11 . The method according to  claim 10 , wherein said cancer is selected from the group consisting of carcinoma, sarcoma, glioma, leukemia and lymphoma. 
     
     
         12 . The method according to  claim 11 , wherein said carcinoma is selected from the group consisting of breast cancer carcinoma, hepatocellular carcinoma and breast adenocarcinoma. 
     
     
         13 . A method for killing cancer cells, inhibiting proliferation of cancer cells or inhibiting cancer cell migration, comprising administering to a subject in need thereof an effective amount of the active agent according to  claim 9 . 
     
     
         14 . The method according to  claim 13 , wherein said cancer cells are selected from the group consisting of carcinoma cells, sarcoma cells, glioma cells, leukemia cells and lymphoma cells. 
     
     
         15 . The method according to  claim 14 , wherein said carcinoma cells are selected from the group consisting of breast cancer carcinoma cells, hepatocellular carcinoma cells and breast adenocarcinoma cells. 
     
     
         16 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier, excipient or diluent and an active agent according to  claim 9 .