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NB4 Cells (nb4 + cell)
Selected AbstractsPML/RAR, fusion protein mediates the unique sensitivity to arsenic cytotoxicity in acute promyelocytic leukemia cells: Mechanisms involve the impairment of cAMP signaling and the aberrant regulation of NADPH oxidase,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2008Lingna Li Acute promyelocytic leukemia (APL) cells are characterized by PML/RAR, fusion protein, high responsiveness to arsenic trioxide (ATO)-induced cytotoxicity and an abundant generation of reactive oxygen species (ROS). In this study we investigated the association among these three features in APL-derived NB4 cells. We found that NADPH oxidase-derived ROS generation was more abundant in NB4 cells compared with monocytic leukemia U937 cells. By using PR9, a sub-line of U937 stably transduced with the inducible PML/RAR, expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML/RAR, fusion protein, since PML/RAR,-expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. On the other hand, the basal intensity of cAMP signaling pathway was compared between NB4 and U937 as well as between PR9 cells with or without PML/RAR,, demonstrating that PML/RAR,-expressing cells had an impaired cAMP signaling pathway which relieved its inhibitory effect on NADPH oxidase derived ROS generation. In summary, the present study demonstrated the correlation of PML/RAR, with cAMP signaling pathway, NADPH oxidase and ROS generation in APL cells. PML/RAR, that bestows NB4 cells various pathological features, paradoxically also endows these cells with the basis for susceptibility to ATO-induced cytotoxcity. J. Cell. Physiol. 217: 486,493, 2008. © 2008 Wiley-Liss, Inc. [source] Andrographolide inhibits growth of acute promyelocytic leukaemia cells by inducing retinoic acid receptor-independent cell differentiation and apoptosisJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2009Shiamala T. Manikam Abstract Objectives The growth inhibiting potential of andrographolide was evaluated in three acute promyelocytic leukaemia cell line models (HL-60, NB4 and all- trans retinoic acid (ATRA)-resistant NB4-R2). Methods In elucidating the mechanisms of growth inhibition, a special emphasis was placed on assessing the induction of differentiation and apoptosis by andrographolide in the primary acute promyelocytic leukaemia NB4 cells. Key findings The compound was 2- and 3-fold more active in inhibiting the growth of HL-60 and NB4-R2 cells compared with NB4 cells, respectively. At IC50 (concentration at which growth of 50% of the cells (compared with medium only treated control cells) is inhibited; 4.5 ,M) the compound exhibited strong cell-differentiating activity in NB4 cells, similar to ATRA (IC50 1.5 ,M). In the presence of a pure retinoic acid receptor antagonist AGN193109, the growth inhibition of NB4 cells by ATRA was reversed, whereas the activity of andrographolide was not affected. This clearly suggested that andrographolide's cell differentiating activity to induce growth inhibition of NB4 cells most likely occurred via a retinoic acid receptor-independent pathway. At higher concentration (2 × IC50), andrographolide was an efficient inducer of apoptosis in NB4 cells. Conclusions Taken together, these results suggest andrographolide and its derivatives, apparently with a novel cell differentiating mechanism and with ability to induce apoptosis, might be beneficial in the treatment of primary and ATRA-resistant acute promyelocytic leukaemia. [source] Antitumor activity and mechanism of action of the iron chelator, Dp44mT, against leukemic cells,AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2009Egarit Noulsri Iron chelators have been reported to induce apoptosis and cell cycle arrest in cancer cells. Recent studies suggest broad and selective antitumor activity of the new iron chelator, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT; Whitnall et al., Proc Natl Acad Sci USA 2006;103:14901,14906). However, little is known concerning its effects on hematological malignancies. Using acute leukemia cells, the effect of Dp44mT on apoptosis, cell cycle, caspase-3 activation, and mitochondrial trans-membrane potential has been examined by flow cytometry. Dp44mT acted to induce a G1/S arrest in NB4 promyelocytic leukemia cells at low concentrations (0.5,2.5 ,M), being far more effective than the clinically used chelator, desferrioxamine (DFO). Moreover, Dp44mT induced apoptosis of NB4 cells in a dose- and time-dependent manner with markedly less effect on nonproliferating cells. The apoptosis-inducing activity of Dp44mT was significantly more effective than DFO. Furthermore, this study also showed that Dp44mT had broad activity, inducing apoptosis in several types of acute leukemia and also multiple myeloma cell lines. Additional studies examining the cytotoxic mechanisms of Dp44mT showed that a reduction in the mitochondrial trans-membrane potential and caspase-3 activation could be involved in the mechanism of apoptosis. Our results suggest that Dp44mT possesses potential as an effective cytotoxic agent for the chemotherapeutic treatment of acute leukemia. Am. J. Hematol. 2009. © 2008 Wiley-Liss, Inc. [source] Wogonin induces the granulocytic differentiation of human NB4 promyelocytic leukemia cells and up-regulates phospholipid scramblase 1 gene expressionCANCER SCIENCE, Issue 4 2008Kun Zhang Previous studies have firmly demonstrated that wogonin, a naturally occurring monoflavonoid extracted from the root of the Chinese herb medicine Scutellaria baicalensis, could effectively inhibit the proliferation of several cancer cell lines. However, little is known about the effect of wogonin on differentiation induction of leukemic cells. Here we investigate the potential role of wogonin in the proliferation and differentiation of NB4, a human promyelocytic leukemia cell line derived from a patient with acute promyelocytic leukemia. Our results indicated that wogonin significantly suppressed the proliferation and efficiently induced the differentiation of NB4 cells. NB4 cell growth was inhibited by 55,60% after treatment with 50 µM wogonin for a period of 5 days. The results of the nitroblue tetrazolium (NBT) reduction test (with 67.13% positive cells by 50 µM wogonin for 5 days), Giemsa staining (with 67.24% positive cells by 50 µM wogonin for 5 days), and the expression of mature-related cell-surface differentiation antigens CD11b and CD14 (with 70.94% CD11b+ and 5.82% CD14+ cells by 50 µM wogonin for 5 days) demonstrated an increase in the differentiation-inducing action of wogonin on the NB4 cells, which was accompanied by an increase in mRNA and protein expression of phospholipids scramblase 1 (PLSCR1). Meanwhile, the level of phosphorylated PKC, (Ser643) was dramatically increased in wogonin treated NB4 cells. Interestingly, wogonin treatment displayed little effect on the apoptosis of NB4 cells. Taken together, the results reported here demonstrated that wogonin could promote the granulocytic differentiation of NB4 cells by up-regulating the expression of PLSCR1 gene. (Cancer Sci 2008; 99: 689,695) [source] | ||||||||||