Sirtuins, NAD-dependent protein deacetylases, play important roles in cellular functions such as metabolism and differentiation. Whether sirtuins function in tumorigenesis is still controversial, but sirtuins are aberrantly expressed in tumors, which may keep cancerous cells undifferentiated. Therefore, we investigated whether the inhibition of sirtuin family proteins induces cellular different...

Small ubiquitin-like modifier (SUMO)/sentrin-specific protease 1 (SENP1), a member of the SENP family, is highly expressed in several neoplastic tissues. However, the effect of SENP1 in acute promyelocytic leukemia (APL) has not been elucidated. In the present study, it was observed that SENP1 deficiency had no effect on the spontaneous apoptosis or differentiation of NB4 cells. Arsenic trioxid...

Acute promyelocytic leukemia (APL) cells, containing the t(15;17) rearrangement, express the fusion protein, PML/ RARa. Clinically, patients respond to all-trans retinoic acid (ATRA) through complete remissions associated with myeloid maturation of leukemic cells. This clinical ATRA response of APL is linked to PML/RARa expression. Unfortunately, these remissions are transient and relapsed APL ...

Treatment of acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA) results in terminal differentiation of leukemic cells toward neutrophil granulocytes. Administration of ATRA leads to massive changes in gene expression, including down-regulation of cell proliferation-related genes and induction of genes involved in immune function. One of the most induced genes in APL NB4 cell...

Recent studies indicate that angiogenesis is important in the pathogenesis of leukemias, apart from its well-established role in solid tumors. In this study, the possible role of angiogenesis in acute promyelocytic leukemia (APL) was explored. Bone marrow trephine biopsies from patients with APL showed significantly increased microvessel density and hot spot density compared with normal control...

BACKGROUND Arsenic trioxide and 1,25-(OH)2D3 (vitamin D3) are used for the treatment of lymphocytic leukemia. However, the effects of combined treatment of these drugs are controversial. In this study, the combined effects of these drugs on the induction of apoptosis in NB4 cells were investigated using the neutral comet assay. METHODS NB4 cells were treated with various doses of arsenic trio...

Programmed cell death-4 (PDCD4) is a recently discovered tumor suppressor protein that inhibits protein synthesis by suppression of translation initiation. We investigated the role and the regulation of PDCD4 in the terminal differentiation of acute myeloid leukemia (AML) cells. Expression of PDCD4 was markedly up-regulated during all-trans retinoic acid (ATRA)-induced granulocytic differentiat...

We have recently reported that PML-RAR-induced misfolding of the N-CoR protein could be reversed by retinoic acid (RA), a therapeutic agent that promotes differentiation of acute promyelocytic leukemia (APL) cells. This finding suggests a role of misfolded N-CoR in the differentiation arrest of APL cells and highlights its significance as a potential molecular target in protein conformation-bas...

2249, and Ro44-4753, respectively. These synthetic retinoids were kindly provided by F. Hoffman-La Roche, Ltd (Basel, Switzerland). Our experiments also showed that the incubation of NB4 cells with the RARa selective agonist, Ro40-6055, induced cell differentiation into neutrophils and apoptosis. These effects were not exerted by Ro48-2249 and Ro44-4753. When NB4 cells were incubated with 0.01 ...

All trans retinoic acid (ATRA), a differentiation inducer for human myeloid NB4 cells, induced accumulation of lipid droplet as determined by positivity of Nile Red and Oil Red O in this cell line. Granulocyte colony-stimulating factor (G-CSF), although not having detectable effect by itself, exerted the additive effects on lipid droplet formation in NB4 cells when combined with ATRA. mRNA anal...