Composition containing arazyme for the prevention and treatment of cancer

Abstract

The present invention relates to a pharmaceutical composition for the prevention and treatment of cancer comprising arazyme as an active ingredient. More precisely, when arazyme produced by Aranicola proteolycius was administered to the nude mice transplanted with human lung carcinoma cell line, weight gaining, inhibition of tumor cell growth and infiltration, and down-regulations of MMP-9, NF-κB and PCNA, were observed. In addition, when arazyme was treated to human breast cancer cells (MDA-MB-231), down regulations of p21, PCNA (Proliferating Cell Nuclear Antigen), VEGF (Vascular Endothelial Growth Factor), BCl2 (B-cell CLL/lymphoma 2), p-p38, PKC (Protein Kinase C) and MMP-1 (Matrix MetalloProteinase-1) which are involved in tumor cell growth, differentiation, proliferation and metastasis, were observed along with the up-regulation of catalase which inhibits tumor development. Therefore, the arazyme can be effectively used as a pharmaceutical composition for the prevention and treatment of cancer.

1 . A pharmaceutical composition for the prevention and treatment of cancer comprising arazyme as an active ingredient. 
     
     
         2 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 1 , wherein the arazyme is selected from the group consisting of:
 (a) a protein containing the amino acid sequence represented by SEQ. ID. NO: 1;   (b) a protein encoded by the DNA containing the coding region of the nucleotide sequence represented by SEQ. ID. NO: 2;   (c) a protein composed of amino acid sequence mutated from the amino acid sequence represented by SEQ. ID. NO: 1 with substitution, deletion, insertion and/or addition of one or more amino acids therein and functionally equal to the protein containing the amino acid sequence represented by SEQ. ID. NO: 1; and   (d) a protein encoded by the DNA hybridized with the DNA containing the nucleotide sequence represented by SEQ. ID. NO: 2 under the strict conditions and functionally equal to the protein containing the amino acid sequence represented by SEQ. ID. NO: 1.   
     
     
         3 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 1 , wherein the arazyme is separated from  Aranicola proteolycius  culture medium. 
     
     
         4 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 3 , wherein the  Aranicola proteolycius  is  Aranicola proteolycius  HY-3 (Accession No: KCTC 0268BP). 
     
     
         5 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 1 , wherein the cancer is selected from the group consisting of lung cancer, breast cancer, liver cancer, stomach cancer, colon carcinoma, brain tumor, pancreas cancer, head carcinoma, cervical cancer, uterine cancer, ovarian cancer, rectal cancer, esophageal cancer, small intestine cancer, anal cancer, fallopian tube carcinoma, endometrical carcinoma, cervix carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, prostatic carcinoma, bladder cancer, kidney cancer, ureter cancer, renal cell carcinoma, pelvic carcinoma and CNS (central nervous system) tumor. 
     
     
         6 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 1 , wherein the arazyme inhibits the expression of MMP-9 (Matrix MetalloProteinase-9). 
     
     
         7 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 1 , wherein the arazyme inhibits the expression of NF-κB (Nuclear Factor κB). 
     
     
         8 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 1 , wherein the arazyme inhibits the expression of PCNA (Proliferating Cell Nuclear Antigen). 
     
     
         9 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 1 , wherein the arazyme inhibits the expression of p21. 
     
     
         10 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 1 , wherein the arazyme inhibits the expression of VEGF (Vascular Endothelial Growth Factor). 
     
     
         11 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 1 , wherein the arazyme inhibits the expression of BCl2 (B-cell CLL/lymphoma 2). 
     
     
         12 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 1 , wherein the arazyme inhibits the expression of p-p38. 
     
     
         13 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 1 , wherein the arazyme inhibits the expression of PKC (Protein Kinase C). 
     
     
         14 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 1 , wherein the arazyme inhibits the expression of MMP-1 (Matrix MetalloProteinase-1). 
     
     
         15 . The pharmaceutical composition for the prevention and treatment of cancer according to  claim 1 , wherein the arazyme stimulates the expression of catalase. 
     
     
         16 . A method for treating cancer comprising administering a pharmaceutically effective dose of arazyme to a subject with cancer. 
     
     
         17 . A method for preventing cancer comprising administering a pharmaceutically effective dose of arazyme to a subject. 
     
     
         18 . (canceled) 
     
     
         19 . A health food for the prevention and improvement of cancer containing a  Aranicola proteolycius  culture medium or arazyme separated from the  Aranicola proteolycius  as an active ingredient. 
     
     
         20 . The health food for the prevention and improvement of cancer according to  claim 19 , wherein the  Aranicola proteolycius  is  Aranicola proteolycius  HY-3 (Accession No: KCTC 0268BP). 
     
     
         21 . The health food for the prevention and improvement of cancer according to  claim 19 , wherein the arazyme is selected from the group consisting of:
 (a) a protein containing the amino acid sequence represented by SEQ. ID. NO: 1;   (b) a protein encoded by the DNA containing the coding region of the nucleotide sequence represented by SEQ. ID. NO: 2;   (c) a protein composed of amino acid sequence with substitution, deletion, insertion and/or addition of one or more amino acids of the amino acid sequence represented by SEQ. ID. NO: 1 and functionally equal to the protein containing the amino acid sequence represented by SEQ. ID. NO: 1; and   (d) a protein encoded by the DNA hybridized with the DNA containing the nucleotide sequence represented by SEQ. ID. NO: 2 under the strict conditions and functionally equal to the protein containing the amino acid sequence represented by SEQ. ID. NO: 1.   
     
     
         22 . The health food for the prevention and improvement of cancer according to  claim 19 , wherein the cancer is selected from the group consisting of lung cancer, breast cancer, liver cancer, stomach cancer, colon carcinoma, brain tumor, pancreas cancer, head carcinoma, cervical cancer, uterine cancer, ovarian cancer, rectal cancer, esophageal cancer, small intestine cancer, anal cancer, fallopian tube carcinoma, endometrical carcinoma, cervix carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, prostatic carcinoma, bladder cancer, kidney cancer, ureter cancer, renal cell carcinoma, pelvic carcinoma and CNS (central nervous system) tumor.