Abstract：
:We previously reported that the thermosensitivity of tumor cells can be increased when the intracellular pH is lowered by inhibiting Na+/H+ exchange through the plasma membrane with amiloride (3,5-diamino-6-chloro-N-(diamino methylene)pyrazinecarboxamide) or its analogues and HCO3-/Cl-exchange with 4,4-diiothiocyanato-stilbene-2,2'-disulfonic acid. In this study, we investigated the effects of (3-amino-6-chloro-5- (1-homopiperidyl)-N-(diaminomethylene)pyrazine-carboxamide) (HMA), an analogue of amiloride and a potent inhibitor of Na+/H+ exchange, and R(+)-[(5,6-dichloro-2,3,9,9a-tetrahydro-3-oxo-9a-propyl-1H-fluoren -7- yl)oxy]acetic acid [B-3(+)], a potent inhibitor of HCO3-/Cl- exchange, on the thermosensitivity of SCK tumor cells in vitro. We observed that 10 microM of HMA could effectively increase the cell death by heating at 43 degrees in pH 6.6 medium but not in pH 7.5 medium. The B-3(+) at 50 microM alone had no effect on the thermosensitivity of cells, but it increased the thermosensitizing effect of HMA in acidic medium. Our results strongly suggested that a combination of HMA and B-3(+) may preferentially thermosensitize tumors in vivo since the interstitial environment in tumors is acidic relative to that in normal tissues.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Song CW,Lyons JC,Griffin RJ,Makepeace CM,Cragoe EJ Jrsubject
Has Abstractpub_date
1993-04-01 00:00:00pages
1599-601issue
7eissn
0008-5472issn
1538-7445journal_volume
53pub_type
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