Within the field of the design of copper-based drugs with potential therapeutical applications, the evaluation of the antitumor and antiproliferative activities of two Cu(II) tropolone derivatives, [Cu(Trop)Sac] and [Cu(Trop)Cl], both containing the N,N-chelated 4,4′-bishydroxymethyl-2,2′-bipyridine ligand, has been performed using the RKO (RKO-ctr) colon cancer cells and its derivative undergoing stable small interference (si) RNA for HIPK2 protein (RKO-siHIPK2), the latter one with acquisition of pro-invasive capacity. This evidence concerns the gene HIPK2 and colonic neoplasm.