Oral Disinfectants Inhibit Protein-Protein Interactions Mediated by the Anti-Apoptotic Protein BcI-x_L and Induce Apoptosis in Human Oral Tumor Cells

摘要

Significant advances during the last decade in the field of small-molecule modulators of protein-protein interactions have raised general awareness of the fact that the modulation of protein-protein interactions has tremendous potential for both basic and applied science. Some of the most advanced orthosteric inhibitors of protein-protein interactions are currently in clinical trials. Here, we demonstrate that the bisbiguanide oral disinfectants chlorhexidine (the active ingredient of commercially available Chlorhexamed, Chlo-rhexal, Periogard, Corsodyl, and Chlorohex) and alexidine (Esemdent), which have been in human use worldwide for many years, target cancer-linked protein-protein interactions between the anti-apoptotic Bcl-2 family protein Bcl-x_L and its pro-apoptotic binding partners. The compounds are shown to induce apoptosis through the mitochondria-dependent apop-totic pathway in oral tumor cell lines.