DIF-3 is a chemical compound that acts by activating GSK-3β to facilitate the degradation of cyclin D1 and c-Myc, resulting in reduced expression levels of these proteins. In addition, DIF-3 inhibits Wnt/β-catenin signaling pathway-related proteins in DLD-1 cells. This compound exerts a potent antiproliferative effect on the HeLa human cervical cancer cell line by inducing cyclin D1 degradation and inhibiting cyclin D1 mRNA expression [1].

In this study, we examined the effects of six DIF analogues (DIF-1, DIF-2 (which has pentanone in place of hexanone), DIF-3 (dechlorinated form of DIF-1), 2-MIDIF-1 (2-methoxy isomer of DIF-1), DMPH (dechlorinated form of DIF-3), and THPH (4-hydroxy substitution of DMPH)) on DNA synthesis, cell growth, erythroid differentiation, and cytosolic free calcium concentration ([Ca2+]i) in human leukemia K562 cells. DIF-3 proved to be the most potent anti-leukemic agent among them, and the order of potency for causing growth inhibition, erythroid induction, and increases in [Ca2+]iTHPH in all the categories tested. [1] DIF-3 activates GSK-3beta to accelerate the proteolysis of cyclin D1 and that this mechanism is involved in the DIF-3-induced G(0)/G(1) arrest in mammalian cells.[2]