%0 Journal Article
%T Up-regulation of p21 and TNF-¦Á is mediated in lycorine-induced death of HL-60 cells
%A Jing Liu
%A Ji-liang Hu
%A Bi-Wei Shi
%A Yan He
%A Wei-Xin Hu
%J Cancer Cell International
%D 2010
%I BioMed Central
%R 10.1186/1475-2867-10-25
%X When HL-60 cells were treated with different concentration of lycorine, the expression of p21 and TNF-¦Á was up-regulated in a concentration-dependent manner as shown by real-time quantitative reverse transcriptase-polymerase chain reaction and Western blotting. Lycorine also down-regulated p21-related gene expression, including Cdc2, Cyclin B, Cdk2 and Cyclin E, promoted Bid truncation, decreased I¦ÊB phosphorylation and blocked NF-¦ÊB nuclear import. Cytochrome c was released from mitochondria as observed with confocal laser microscopy.The TNF-¦Á signal transduction pathway and p21-mediated cell-cycle inhibition were involved in the apoptosis of HL-60 cells induced by lycorine. These results contribute to the development of new lycorine-based anti-leukemia drugs.A tumor is a disease with two defining characteristics: a proliferation disorder and an apoptosis obstacle. The inhibition of proliferation and the induction of apoptosis are regulated by a network of signaling pathways and transcription factors, which may represent potential targets for rational tumor therapy [1,2]. Apoptotic events are regulated by the interplay of proapoptotic and antiapoptotic proteins. The apoptotic pathways include two major signaling pathways: the death receptor-induced pathway and the mitochondria-apoptosome-mediated pathway. Elements of the death receptor pathway include cell death ligands and their receptors, such as tumor necrosis factor (TNF) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor, and downstream molecules, such as caspase 8. The major components of the mitochondrial pathway include apoptotic stimuli, mitochondria, the apoptosome, and key effector caspases [1]. Crosstalk between these two apoptotic pathways is mediated through the truncation of the BH3-interacting death domain (Bid) protein. Inhibitors of apoptosis proteins include the X-linked inhibitor of apoptosis protein (XIAP), the cellular inhibitor of apoptosis protein (cIAP), survivin,
%U http://www.cancerci.com/content/10/1/25