Enhancement of cell killing and increase in cytosolic calcium concentration by combined treatments with hyperthermia and TMB-8 in mouse mammary carcinoma FM3A cells.
Mouse mammary carcinoma FM3A cells were exposed 42 degrees C or 44 degrees 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 microM. Cell survival, cytosolic calcium ion concentration, [Ca2+]C, and influx of 45Ca2+ were investigated to examine the cardinal role of intracellular Ca2+ in hyperthermic cell killing. The [Ca2+]C in a single cell was measured by a digital image analyzing technique using Fura-2. TMB-8 enhanced cell killing, increase in [Ca2+]C, and influx of 45Ca2+ induced by both hyperthermic treatments. In contrast, TMB-8 abolished the increase in [Ca2+]C induced by hyperthermia at 42 degrees C and 44 degrees C in the absence of extracellular Ca2+. These results suggest that TMB-8, an agent usually called an inhibitor of intracellular calcium mobilization at 37 degrees C or lower, enhances Ca2+ entry from the extracellular space at 42 degrees C or 44 degrees C and, in turn, promotes cell killing under hyperthermic conditions.
Kondo
T
T
Department of Radiation Biophysics, Kobe University School of Medicine, Japan.
Kano
E
E
Habara
Y
Y
Kanno
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002277:Carcinoma / Q000378:metabolism / Q000628:therapy*; D016923:Cell Death / Q000187:drug effects; D003131:Combined Modality Therapy; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006979:Hyperthermia, Induced; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D002118:Calcium