Of the hematological disorders typified by poor prognoses and survival rates, T-cell acute lymphoblastic leukemia (T-ALL) is one of the most commonly diagnosed. Despite the development of new therapeutic agents, the treatment options for this cancer remain limited. In this manuscript, we investigated the anti proliferative effects of plumbagin, mediated by the activation of mitogen-activated protein kinase (MAPK) pathways, and inhibition of NF-kappa B signaling; the human T-ALL MOLT-4 cell line was used as our experimental system. Plumbagin is a natural, plant derived compound, which exerts an anti-proliferative activity against many types of human cancer. Our experiments confirm that plumbagin induces a caspase-dependent apoptosis of MOLT-4 cells, with no significant cytotoxicity seen for normal peripheral blood mononuclear cells (PBMCs). Plumbagin also inhibited LPS-induced phosphorylation of p65, and the transcription of NF-kappa B target genes. Our results now show that plumbagin is a potent inhibitor of the NF-kappa B signaling pathway, and suppressor of T-ALL cell proliferation. (C) 2016 Published by Elsevier Inc.