Methods for regulating cell mitosis by inhibiting serine/threonine phosphatase

Abstract

Disclosed herein are methods of inhibiting proliferation of a cancer cell or inducing apoptosis of a cancer cell, which does not overexpress N—CoR. Also disclosed herein are methods of inhibiting proliferation or inducing apoptosis of a cancer cell that overexpresses TCTP and methods for determining whether a compound is effective in inducing cell death.

1 - 23 . (canceled) 
     
     
         24 . A method for reducing the amount of TCTP in a cell comprising contacting the cell with an effective amount of a protein phosphatase 2A inhibitor, thereby reducing the amount of TCTP in the cell. 
     
     
         25 . The method of  claim 24 , wherein the cell is a cancer cell. 
     
     
         26 . The method of  claim 25 , wherein the cancer is adrenocortical cancer, bladder cancer, osteosarcoma, cervical cancer, esophageal, gallbladder, head and neck cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, renal cancer, melanoma, pancreatic cancer, rectal cancer, thyroid cancer, throat cancer, breast cancer, lung cancer and prostate cancer. 
     
     
         27 . The method of  claim 24 , wherein the protein phosphatase 2A inhibitor has the structure: 
       
         
           
           
               
               
           
         
         or a salt, enantiomer or zwitterion of the compound. 
       
     
     
         28 . A method for determining whether a compound is effective in inducing cell death in a cancer cell comprising:
 (a) contacting a first cancer cell with the compound;   (b) determining the level of expression of TCTP in the first cancer cell;   (c) contacting a second cancer cell with a protein phosphatase 2A inhibitor;   (d) determining the level of expression of TCTP in the second cancer cell;   (e) comparing the level of expression of TCTP determined in step (b) with the level determined in step (d),   wherein, when the level of expression determined in step (b) is equal to, or lower than, the level of expression determined in step (d), the compound is effective to induce cell death.   
     
     
         29 . The method of  claim 28 , wherein the cancer is adrenocortical cancer, bladder cancer, osteosarcoma, cervical cancer, esophageal, gallbladder, head and neck cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, renal cancer, melanoma, pancreatic cancer, rectal cancer, thyroid cancer, throat cancer, breast cancer, lung cancer and prostate cancer. 
     
     
         30 . The method of  claim 28 , wherein the protein phosphatase 2A inhibitor has the structure: 
       
         
           
           
               
               
           
         
         or a salt, enantiomer or zwitterion of the compound. 
       
     
     
         31 . A method for predicting whether treatment of a subject with an agent will be successful in treating a subject suffering from cancer comprising:
 (a) obtaining a sample comprising cancer cells from the subject;   (b) culturing the cancer cells;   (c) determining the level of expression of TCTP in the cancer cells;   (d) contacting the cancer cells with the agent;   (e) determining the level of expression of TCTP in the cancer cells;   (f) comparing the level of expression of TCTP determined in step (c) with the level of expression determined in step (e),   wherein, when the level of expression determined in step (c) is lower than the level of expression determined in step (e) predicts that treatment of the subject with the agent will be successful in treatment of the cancer.