THE SIGMA-RECEPTOR LIGAND, REDUCED HALOPERIDOL, INDUCES APOPTOSIS ANDINCREASES INTRACELLULAR-FREE CALCIUM LEVELS [CA2+](I) IN COLON AND MAMMARY ADENOCARCINOMA CELLS

The sigma receptor ligand reduced haloperidol (50 and 100 mu M), poten tly inhibited cell proliferation, and induced apoptosis in WIDr colon and MCF-7 adenocarcinoma cell lines. Apoptosis was confirmed after dru g treatment of the cells by the presence of nuclear fragmentation afte r staining of the cells with Hoechst 33258 and cellular DNA fragmentat ion ELISA and by condensation of the heterochromatin using transmissio n electron microscopy. However, internucleosomal DNA cleavage was not detected using gel electrophoresis. Reduced haloperidol (100 mu M) inc reased the intracellular free calcium levels [Ca2+](i) in both cell li nes, which was independent of extracellular calcium. suggesting that t he rise in [Ca2+](i) was from intracellular stores and that an increas e in [Ca2+], may act as a ''trigger'' for apoptosis in these Cell line s. (C) 1996 Academic Press, Inc.