<p><b>A, B</b> Sigma-2/PGRMC1 agonist siramesine causes dose-dependent activation of caspase 3 in primary neuronal cultures (<b>A</b>) and in SKOV-3 human ovarian cancer cells (<b>B</b>) but sigma-2/PGRMC1 antagonists RHM-1, CT0109 and CT0093 do not. <b>C</b>, <b>D</b> Sigma-2/PGRMC1 agonists siramesine, WC-26 and SV-119 cause dose-dependent cell death in primary hippocampal/cortical cultures (<b>C</b>) and in SKOV-3 human ovarian cancer cells (<b>D</b>) but sigma-2/PGRMC1 antagonists RHM-1, CT0109 and CT0093 do not, except at very high concentrations (>100 µM). (<b>E</b>) Treatment of cultures of hippocampal and cortical cells with 20 to 80 µM SV-119 for 24 hours induced the activation of caspase 3/7 (*p<0.05 by 2-tailed Student's t-test compared to control). Co-treatment of cultures with 40 µM CT0109 or CT0093 did not increase caspase activity and blocked the activation by the agonist SV-119.</p
