To this end, we challenged human embryonic kidney 293 (HEK293) and colon cancer DLD1 cell lines with a panel of metal ions, and observed that copper (Cu), but with a much lesser extent of the other ions we examined, including Zn2+(ZnCl2), Fe3+(Fe(NO3)3), Ni2+(Ni(NO3)2), Ag+(AgNO3), Li+(LiCl), Mn2+(MnCl2), Ca2+(CaCl2), and Mg2+(MgCl2), could significantly elevate AKT kinase activity indicated by the increase of AKT phosphorylation at Thr308 and Ser473, as well as its downstream substrate glycogen synthase kinase 3 beta (GSK3β) phosphorylation (Figure 1a; Figure S1a, Supporting Information). Here, GSK3B is linked to malignant colon neoplasm.