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Title: Effects of amiloride on thermosensitivity of Chinese hamster cells under neutral and acidic pH

Journal Article · · Cancer Res.; (United States)
OSTI ID:5737187

The modifying effects of amiloride on the thermosensitivity of Chinese hamster V-79 cells were examined under both neutral (pH 7.3) and acidic (pH 6.6) conditions. Amiloride, a diuretic drug, is known to inhibit the Na+/H+ exchange activity. Under the extracellular pH of 7.3, amiloride (0.1-0.5 mM) enhanced the thermal cell killing powers of 42/sup 0/C hyperthermia with increasing concentration and exposure time of the drug. The age response of cells to 42/sup 0/C hyperthermia in the presence or absence of amiloride (0.5 mM) showed that amiloride sensitized cells to heat, especially those at G1-S boundary through middle S phases. On the other hand, the lowering of extracellular pH to 6.6 enhanced cell killing by 42/sup 0/C hyperthermia. When cells were exposed to 42/sup 0/C hyperthermia in the presence of amiloride at pH 6.6, cell survival decreased still more. The thermosensitizing effects of the lowered pH at 6.6 and amiloride appeared to be additive. From these results, it is suggested that the thermosensitization by amiloride is probably due, in part, to the inhibition of cellular Na+/H+ exchange activity. The present study proposes the possibility that amiloride may be useful as a hyperthermic sensitizer in a clinical treatment of cancer.

Research Organization:
Kyoto Univ., Japan
OSTI ID:
5737187
Journal Information:
Cancer Res.; (United States), Journal Name: Cancer Res.; (United States)
Country of Publication:
United States
Language:
English