Abstract
Mouse mammary carcinoma FM3A cells were exposed 42°C or 44°C hyperthermia for 60 min in a culture medium with or without 8-(N,N-diethylamino) octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) at a concentration of 100 μM. Cell survival, cytosolic calcium ion concentration, [Ca 2+] c, and influx of 45Ca 2+ were investigated to examine the cardinal role of intracellular Ca 2+ in hyperthermic cell killing. The [Ca 2+] c in a single cell was measured by a digital image analyzing technique using Fura-2. TMB-8 enhanced cell killing, increase in [Ca 2+] c, and influx of 45Ca 2+ induced by both hyperthermic treatments. In contrast, TMB-8 abolished the increase in [Ca 2+] c induced by hyperthermia at 42°C and 44°C in the absence of extracellular Ca 2+. These results suggest that TMB-8, an agent usually called an inhibitor of intracellular calcium mobilization at 37°C or lower, enhances Ca 2+ entry from the extracellular space at 42°C or 44°C and, in turn, promotes cell killing under hyperthermic conditions.
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