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

Carly Griffin,Caroline Hamm,James Mcnulty,Siyaram Pandey

doi:10.1186/1475-2867-10-6

Abstract

BackgroundPancratistatin, a natural compound extracted from Hymenocallis littoralis, can selectively induce apoptosis in several cancer cell lines. In this ex vivo study, we evaluated the effect of pancratistatin on peripheral blood mononuclear cells obtained from 15 leukemia patients prior to clinical intervention of newly diagnosed patients, as well as others of different ages in relapse and at various disease progression states.ResultsMononuclear 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.ConclusionOur results show that pancratistatin is an effective and selective anti-cancer agent with potential for advancement to clinical trials.

Highlights

Pancratistatin, a natural compound extracted from Hymenocallis littoralis, can selectively induce apoptosis in several cancer cell lines
Patients were diagnosed in the clinic with: Acute Myeloid Leukemia (AML), subtyped as M0 - M7 or MDS; Acute Monocytic Leukemia (AMoL); Acute Lymphoblastic Leukemia (ALL), subtyped as Burkitt's (L3); Chronic Myelogenous Leukemia (CML); or Chronic Myelomonocytic Leukemia (CMML)
Response to chemotherapy administered in the clinic is indicated as complete response (CR), partial response (PR), no response (NR), relapsed or censored

Summary

Introduction

Pancratistatin, a natural compound extracted from Hymenocallis littoralis, can selectively induce apoptosis in several cancer cell lines. In this ex vivo study, we evaluated the effect of pancratistatin on peripheral blood mononuclear cells obtained from 15 leukemia patients prior to clinical intervention of newly diagnosed patients, as well as others of different ages in relapse and at various disease progression states. 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]. 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. Clinical leukemia and non-cancerous peripheral blood mononuclear cells (ncPBMCs) were treated with pan-

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Conclusion