Pancratistatin induces apoptosis in clinical leukemia samples with minimal effect on non-cancerous peripheral blood mononuclear cells

Mononuclear cells from healthy volunteers and leukemia patients were exposed to 1 μM pancratistatin for up to 48 h. Irrespective of leukemia type, pancratistatin induced apoptosis in the leukemic samples, with minimal effects on non-cancerous peripheral blood mononuclear control cells.Our results show that pancratistatin is an effective and selective anti-cancer agent with potential for advancement to clinical trials.Chemotherapy for acute myeloid leukemia, despite earnest attempts, has not significantly changed in the last 30 years. Treatment continues to be based on the cytotoxic chemotherapies of anthracyclines and cytarabine. The natural compound, pancratistatin, extracted from the Hymenocallis littoralis, has broad-range efficacy against several cancer cell lines at 1 μM, with minimal effect on non-cancerous cell lines of the same origin [1,2]. Pancratistatin treatment causes phosphatidyl-serine flipping, caspase-3 activation, generation of reactive oxygen species (ROS), and loss of mitochondrial membrane potential, which leads to apoptosis in cultured T-cell (Jurkat) leukemia cells [3]. Although pancratistatin is a non-genotoxic drug, its target has not yet been elucidated [3,4]. The efficacy of pancratistatin in inducing apoptosis selectively in cultured (commercial) cancer cell lines is well established, though its effect on leukemia cells obtained from patients has not been tested. In this study, clinical leukemia and non-cancerous peripheral blood mononuclear cells (ncPBMCs) were treated with pancratistatin to determine its selectivity and efficacy to induce apoptosis ex vivo. Activity of pancratistatin was compared to that of the widely used chemotherapeutic, paclitaxel, against cancer cells. Peripheral blood samples from patients with a diagnosis of acute myeloid leukemia (AML; n = 11), acute lymphoid leukemia (ALL; n = 1), chronic myelogenous leukemia (CML; n = 1), chronic myelomonocytic leukemia (CMML; n = 1) and Mantle cell lymphoma (n = 1) were obtai