Nonactin #76040

The antibiotic Nonactin is an ionophore that binds and transports monovalent cations (e.g., K⁺, NH4⁺, and Na⁺) across membranes through passive diffusion (1). Nonactin displays both antibacterial and anti-tumor activities, and inhibits drug efflux in multiple drug resistant cancers (2). Naturally occurring Nonactin is composed of four monomers of Nonactic acid, comprised of an equal number of (+) and (-) monomers. The antibiotic properties of Nonactin result from its ability to form stable complexes with monovalent cations; artificial Nonactin tetramers, comprised of either all (+) or all (-) Nonactic acid monomers, lack ion binding ability and are less potent antibiotics (3). Treatment of erythrocytes with Nonactin leads to suicidal erythrocyte death as evidenced by the shrinking of erythrocytes and translocation of phosphatidylserine from the erythrocyte interior to the cell surface (4). Nonactin selectively induces apoptosis and results in tumor regression in a β-catenin mutant HCT 116 xenograft model (5), and can inhibit the surface expression of endogenous HSP60 (6).