Background:

Difopein is an inhibitor of 14-3-3 protein.

14-3-3 protein has been involved in a wide range of biologic processes such as signal transduction, vesicular transport, cell cycle control, DNA replication, DNA repair and apoptosis. 14-3-3 protein has been associated with tumor genesis. 14-3-3 protein correlates with reduced tumor cell apoptosis and abbreviated patient survival. Up-regulation of 14-3-3 protein provides a survival advantage to tumor cells. Inhibition of 14-3-3 protein might trigger apoptosis, inhibit growth of established tumors, suppress de novo tumor formation, and promise a novel therapeutic approach for glioma treatment [1].

In human glioma U251 and U87 cells, difopein resulted in apoptosis characteristics, such as nuclear fragmentation, DNA laddering fragment and appearance of membrane-enclosed apoptotic bodies. Difopein induced apoptosis in a time-dependent manner [1]. Difopein induced glioma cell apoptosis through down-regulating Bcl-2, up-regulating Bax and activating caspase-9 and caspase-3. In vivo, difopein effectively hindered proliferation and triggered apoptosis of tumor cells implanted into nude mice [1].

Reference:
[1] Cao W, Yang X, Zhou J, et al.  Targeting 14-3-3 protein, difopein induces apoptosis of human glioma cells and suppresses tumor growth in mice[J]. Apoptosis, 2010, 15(2): 230-241.