Composition for autophagy inhibiting in cell, and pharmaceutical composition for preventing or treating neoplastic disease or inhibiting anti-cancer agents resistance containing the same

Abstract

Provided are a polypeptide having the activity of inhibiting autophagy in a cell, a composition for inhibiting autophagy in a cell, and particularly in a tumor cell, containing the polypeptide as an active ingredient, and a pharmaceutical composition containing the polypeptide, and more specifically, a composition for inhibiting autophagy in a cell containing a polypeptide inhibiting the control mechanism of autophagy as an active ingredient, and a pharmaceutical composition for preventing or treating a neoplastic disease or for inhibiting resistance to anticancer agents, containing the polypeptide.

What is claimed is: 
     
         1 . A polypeptide having the activity of inhibiting autophagy in a cell, represented by the General Formula of a sequence below:
   X3-X1-T-X1-K-X2   [General Formula]
   wherein, in General Formula of a sequence above,   T is threonine,   K is lysine;   X1 is at least one amino acid selected from the group consisting of alanine, glycine, isoleucine, leucine, methionine, proline, and valine;   X2 is at least one amino acid selected from the group consisting of alanine, threonine, cysteine, asparagine, proline, glutamine, and serine; and   X3 is at least one amino acid selected from the group consisting of alanine, glutamine, threonine, serine, asparagine, and glycine, or is absent.   
     
     
         2 . The polypeptide of  claim 1 ,
 wherein X1 and X2 are alanine.   
     
     
         3 . The polypeptide of  claim 1 ,
 wherein X1 is proline; and X2 is threonine.   
     
     
         4 . The polypeptide of  claim 1 ,
 wherein X1 is isoleucine; and X2 is threonine.   
     
     
         5 . The polypeptide of  claim 1 ,
 wherein X3 is glutamine or threonine.   
     
     
         6 . The polypeptide of  claim 1 ,
 wherein X3 is serine.   
     
     
         7 . The polypeptide of  claim 1 ,
 wherein X3 is glycine, asparagine, or threonine.   
     
     
         8 . The polypeptide of  claim 1 ,
 wherein the polypeptide inhibits autophagy in a cell by reducing the expression of at least one protein selected from the group consisting of p-AMPK, ATG5-ATG12, Beclin1, p-Beclin1, LC3-I, and LC3-II.   
     
     
         9 . The polypeptide of  claim 1 ,
 wherein the polypeptide inhibits autophagy in a cell by increasing the expression of p-mTOR or p62 protein.   
     
     
         10 . The polypeptide of  claim 1 ,
 wherein the polypeptide is labeled with any one labeling material selected from the group consisting of chromogenic enzymes, radioisotopes, chromophores, luminescent materials, fluorescers, magnetic resonance imaging (MRI) materials, super paramagnetic particles, and ultrasuper paramagnetic particles.   
     
     
         11 . The polypeptide of  claim 1 ,
 wherein the cell is a tumor cell.   
     
     
         12 . A composition for inhibiting autophagy in a cell comprising the polypeptide of  claim 1  as an active ingredient. 
     
     
         13 . A pharmaceutical composition for preventing or treating a neoplastic disease comprising the polypeptide of  claim 1  as an active ingredient. 
     
     
         14 . The pharmaceutical composition of  claim 13 ,
 wherein the neoplastic disease is selected from the group consisting of lung cancer, liver cancer, colon cancer, pancreatic cancer, stomach cancer, breast cancer, ovarian cancer, kidney cancer, thyroid cancer parathyroid cancer, esophageal cancer, prostate cancer, brain cancer, skin cancer, osteosarcoma, soft tissue sarcoma, glioma, lymphoma, nasopharyngeal cancer, larynx cancer, adrenal gland cancer, colon carcinoma, ureteral cancer, gallbladder cancer, bladder cancer, testis cancer, uterine cervical cancer, endometrial cancer, choriocarcinoma, head and neck cancer, malignant melanoma, leukemia, multiple myeloma, chronic myeloid leukemia, neuroblastoma, and aplastic anemia.   
     
     
         15 . A pharmaceutical composition for inhibiting resistance to anticancer agents, comprising the polypeptide of  claim 1  as an active ingredient. 
     
     
         16 . The pharmaceutical composition of  claim 15 ,
 wherein the composition has resistance to at least one anticancer agent selected from the group consisting of erlotinib, celastrol, cisplatin, docetaxel, osimertinib, taxol, pemetrexed, and tamoxifen.