Interactions of hyperthermia and drugs: treatments and probes

At temperatures above 37 degrees C, the abilities of many, but not of all, anticancer drugs to kill cells increases substantially. The increased cytotoxic rate can vary smoothly with temperature (e.g., nitrosoureas or cis-platinum(II) diamminedichloride) or show a marked threshold near 43 degrees C (e.g., adriamycin or bleomycin). Clinically, the increased cell killing rate can be used in the combination of localized hyperthermia and systemic chemotherapy. Drugs can also be useful in the study of cell killing by heat. Aliphatic alcohols which mimic and interact with heat, tend to be localized in lipid-rich regions of the cell, i.e., membranes. Heat modifies the rate at which plant lectins agglutinate cells and also modifies capping rates; most likely, these changes reflected membrane alterations. Because other data strongly imply that proteins are involved in cell death, we think that the first step in hyperthermic killing of cells involves damage to specific membrane-associated proteins.