The Sigma Receptor Ligand, Reduced Haloperidol, Induces Apoptosis and Increases Intracellular-Free Calcium Levels [Ca2+]iin Colon and Mammary Adenocarinoma Cells

The sigma receptor ligand reduced haloperidol (50 and 100μM), potently inhibited cell proliferation, and induced apoptosis in WIDr colon and MCF-7 adenocarcinoma cell lines. Apoptosis was confirmed after drug treatment cells by the presence of nuclear fragmentation after staining of the cells with Hoechst 33258 and cellular DNA fragmentation ELISA and by condensation of the heterochromatin using transmission electron microscopy. However, internucleosomal DNA cleavage was not detected using gel electrophoresis. Reduced haloperidol (100 μM) increased the intercellular free calcium levels [Ca2+]iin both cell lines, which was independent of extracellular calcium, suggesting that the rise in [Ca2"]iwas from intracellular stores and that an increase in [Ca2+]imay act as a "trigger" for apoptosis in these cell lines.