SULOFENUR CYTOTOXICITY AND CHANGES IN CYTOSOLIC CALCIUM AND MITOCHONDRIAL-MEMBRANE POTENTIAL IN HUMAN COLON ADENOCARCINOMA CELL-LINES

Sulofenur treatment (12.5 mu M-1 mM) of colon adenocarcinoma cell lines resulted in dose- and time-dependent cell killing, LYc(5) cells were viable longer than GC(3)/c(1) cells. Each concentration resulted in elevation of cytosolic calcium [Ca2+](i)) for both cell lines. At lower doses, elevation was delayed for LYc(5) cells, GC(3)/c(1) cells after 1 mM treatment in Ca2+-free HBSS showed no rise of [Ca2+](i). GC(3)/c(1) cells after carbonyl cyanide-m-chlorophenylhydrazone rapidly lost rhodamine 123 fluorescence from mitochondria; after 1 mM sulofenur, fluorescence faded slowly. Following treatment, cells became rounded, blebs formed and the cells died. Results suggest that elevated [Ca2+](i) plays an important role in sulofenur cytotoxicity.