ALLOSTERIC REGULATION OF GSK-3 BY SMALL MOLECULES IN HUMAN COLONIC EPITHELIAL CELLS IN THE STUDY OF COLON CANCER

Abstract

GSK-3 is a prominent protein in colon cancer that regulates how colon cells proliferate and differentiatefrom the stem cell stage. Its unique structure containing seven pockets for potential binding makes GSK-3 a promising target for drugs that could prevent cell proliferation in colon cancercells. This study examined the effects various small molecules can have on regulating GSK-3 when the molecules are used to treat colon cancer cells. Since GSK-3 effects whether or not the protein β-cateninis degraded, the activity of GSK-3 was indirectly measuredby examining changes in the β-cateninprotein levels. As β-cateninlevels were seen to increase or decrease, hypotheses could be made regarding if and how each small molecule was affecting GSK-3 andwhat the implications could mean for colon cancer. While many of the results are inconclusive and require further testing, some compounds of interest stood out as having potential activating or deactivating effects on GSK-3. Future experiments consisting ofvarious types of assays and testing of additional cell lines will likely reveal more about each of these compounds’ effecton GSK-3.