Interaction of amphotericin B and 43 degrees hyperthermia

Abstract

At 43 degrees (but not at 41 degrees), the polyene antibiotic amphotericin B effectively inactivates mammalian cells in vitro even at doses which are used prophylactically, routinely, and continuously in some tissue culture laboratories. The greatly enhanced killing may reflect interactions between the drug and hyperthermia at the level of the cells' plasma membrane. A similar enhancement of cell killing at 43 degrees was seen when cells were exposed to nonisotonic salt solutions. Another polyene, nystatin, shows no temperature dependence, at least over the dose range examined, while another antifungal agent, polymyxin B, does so only at very high doses. The in vitro thermosensibility of cells to amphotericin B is reflected in vivo: EMT-6 murine tumor cells were killed much more efficiently in situ at 43 than at 37 degrees. Amphotericin B may be a useful agent in multiple drug thermochemotherapy.