Jurate Savickiene

Jurate Savickiene
Vilnius University · Department of Molecular Cell Biology

PhD

About

38
Publications
3,924
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662
Citations
Citations since 2016
3 Research Items
307 Citations
2016201720182019202020212022020406080
2016201720182019202020212022020406080
2016201720182019202020212022020406080
2016201720182019202020212022020406080

Publications

Publications (38)
Article
Human amniotic fluid (AF)-derived mesenchymal stem cells (MSCs) sharing embryonic and adult stem cells characteristics are interesting by their multipotency and the usage for regenerative medicine. However, the usefulness of these cells for revealing the fetal diseases still needs to be assessed. Here, we have analyzed the epigenetic environment in...
Article
Xenograft models are suitable for in vivo study of leukemia’s pathogenesis and the preclinical development of anti-leukemia agents but understanding of epigenetic regulatory mechanisms linking to adult cell functions in pathological conditions during different in vivo treatments is yet unknown. In this study, for the first time epigenetic chromatin...
Article
Full-text available
Human amniotic-fluid-derived mesenchymal stem cells (AF-MSCs) are interesting for their multilineage differentiation potential and wide range of therapeutic applications due to the ease of culture expansion. However, MSCs undergo replicative senescence. So far, the molecular mechanisms that underlie fetal diseases and cell senescence are still poor...
Article
Full-text available
Human amniotic fluid stem cells have become an attractive stem cell source for potential applications in regenerative medicine and tissue engineering. The aim of this study was to characterize amniotic fluid-derived mesenchymal stem cells (AF-MSCs) from second- and third-trimester of gestation. Using two-stage protocol, MSCs were successfully cultu...
Data
Proteome differences associated with myogenic, adipogenic, osteogenic, and neurogenic differentiation of late second-trimester AF-MSCs are presented in Supplementary Table 1 (see Supplementary Table 1 in Supplementary Material available online at http://dx.doi.org/10.1155/2015/319238). For a comparison of the proteome profile, we presented a sample...
Article
Therapeutic strategies targeting histone deacetylase (HDAC) inhibition have become promising in many human malignancies. Belinostat (PXD101) is a hydroxamate-type HDAC inhibitor tested in phase I and II clinical trials in solid tumors and hematological cancers. However, little is known about the use of belinostat for differentiation therapy against...
Article
Full-text available
Epigenetic regulation is known to affect gene expression, and recent research shows that aberrant DNA methylation patterning and histone modifications may play a role in leukemia-genesis. In order to highlight the co-operation of epigenetic mechanisms acting during the latter process it is important to clarify their potential as biomarkers of granu...
Article
Epigenetic silencing of cancer-related genes by abnormal methylation and the reversal of this process by DNA methylation inhibitors represents a promising strategy in cancer therapy. As DNA methylation affects gene expression and chromatin structure, we investigated the effects of novel DNMT (DNA methyltransferase) inhibitor, RG108, alone and in it...
Article
Full-text available
DNMT inhibitors are promising new drugs for cancer therapies. In this study, we have observed the antileukemic action of two diverse DNMT inhibitors, the nucleoside agent zebularine and the non-nucleoside agent RG108, in human promyelocytic leukemia (PML) HL-60 cells. Zebularine but not RG108 caused dose- and time-dependent cell growth inhibition a...
Article
Full-text available
Aberrant DNA methylation is a critical epigenetic process involved in gene expression of tumor cells. Diverse DNA methyltransferase inhibitors are being studied as potential anticancer drugs, and there is interest in developing novel and more effective DNMTIs. We evaluated zebularine, a stable and low-toxic cytidine analog, effects on human promyel...
Article
C/EBPα and PU.1 are the basic transcription factors that control differentiation-related genes, including granulocyte- colony-stimulating factor (G-CSFR) and human neutrophil elastase (HNE). Here, we analyzed a role of C/EBPα and PU.1 in human acute leukemia cell lines, HL-60 and NB4, in association with a modified chromatin structure by histone de...
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The biological effects of low-dose radiation have attracted attention, but data are currently insufficient to fully understand the beneficial role of the phenomenon. In the present study, we have investigated the effects of low doses of gamma-irradiation alone and in combination with all-trans-retinoic acid (RA) on proliferation, apoptosis and diff...
Article
Full-text available
The modifications of intracellular redox balance leads to important cellular changes in many cell types. Here, a causal relationship among redox state, granulocytic differentiation induced by all-trans retinoic acid (RA) or dibutyryl cAMP (dbcAMP) and apoptosis have been studied in the human acute promyelocytic leukaemia HL-60 cells. The modulation...
Article
Human dental pulp derived from exfoliated deciduous teeth has been described as a promising alternative source of multipotent stem cells. While these cells share certain similarities with mesenchymal stem-like cells (MSC) isolated from other tissues, basically they are still poorly characterized. In this study, for the first time, a proteomic map o...
Article
Acute promyelocytic leukemia KG1 cells with t(11;17) PLZF-RARalpha respond poorly to the differentiation inducer all-trans retinoic acid (RA), and the reason for the RA resistance is the recruitment of histone deacetylase by PLZF-RARalpha. Here, we demonstrate that histone deacetylase inhibitors (HDACIs), FK228, BML-210, phenyl butyrate, and vitami...
Article
Full-text available
Histone deacetylase inhibitors (HDACI) have been shown to inhibit cancer cell proliferation, induce cell cycle arrest, and stimulate apoptosis. To date, the key apoptotic proteins and pathways necessary for the anti-tumor activities of HDACI remain ill-defined, and the specific genes regulated by HDACI to mediate these effects have not been fully d...
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Despite the understanding of the importance of phosphoinositide 3-kinase (PI 3-K) signaling pathway in the regulation of cellular proliferation, little is known about its role during phorbol 12-myristate 13-acetate (PMA)-induced differentiation in human leukemia cells. Here, we report a novel finding that PI 3-K inhibition by LY294002 significantly...
Article
Water-soluble vitamin B3, niacin, and its related compounds were suggested to be applicable for medical use. In this article, we examined the anti-leukemic effects of two distinct histone deacetylase (HDAC1 and Sir2) inhibitors, sodium phenyl butyrate (PB) and vitamin B3, respectively, on human promyelocytic leukemia cells HL-60, using HDACIs alone...
Article
FK228 (depsipeptide) is a novel histone deacetylase inhibitor (HDACI) that has shown therapeutical efficacy in clinical trials for malignant lymphoma. In this article, we examined in vitro effects of FK228 on human leukemia cell lines, NB4 and HL-60. FK228 alone (0.2-1 ng/mL) inhibited leukemia cell growth in a dose-dependent manner and induced dea...
Article
Histone deacetylase inhibitors have a potent role in the strategy for the treatment of leukemias. BML-210 (N-(2-Aminophenyl)-N' phenyloctanol diamine) is the novel histone deacetylase inhibitor, and its mechanism of action has not been characterized. In this study, we examined the in vitro effects of BML-210 on the human leukemia cell lines (NB4, H...
Article
The molecular mechanisms of the cellular response to different apoptotic effectors are only partially understood. Herein, the role of transcription factors, Sp1 and NFkappaB in differentiation-related and etoposide-induced apoptosis was examined in a number of human leukemia cell lines (HL-60, NB4, HEL, THP-1, K562). This was investigated with resp...
Article
DNA topoisomerase inhibitors induce a specific signaling cascade that promotes an active apoptotic caspase-dependent cell death process. However, little is known about the initial signals elicited by these agents. In the present study, we compared apoptosis in HL-60 cells treated either with the chemotherapeutic drug etoposide (VP16) alone or combi...
Article
Treatment of human acute promyelocytic leukemia cells with phorbol 12-myristate 13-acetate (PMA) results in growth arrest and differentiation toward monocytes, which subsequently die by apoptosis. However, the relationship between terminal differentiation and apoptosis remains unclear. Here we have studied Sp1 and nuclear factor kappaB (NF-kappaB)...
Article
Full-text available
Many eukaryotic proteins contain both O-and N-linked N-acetylgluco-samine groups. The effects of O-and N-glycosylation on the growth and differentiation of the human promyelocytic leukemia cell line HL-60 have been studied to examine whether the glycosylation of nuclear pro-teins is needed for HL-60 cells to differentiate into granulocyte-like cell...
Article
Therapeutic nucleoside analogue 3-deazauridine (DU) exerts cytotoxic activity against cancer cells by disruption of DNA synthesis resulting in cell death. The present study evaluates whether DU alone at doses 2.5-15 microM or in combination with all trans retinoic acid (RA) or dibutyryl cAMP (dbcAMP) is effective against myelogenous leukemia. The d...
Article
Full-text available
During the systemic inflammatory response, circulating cytokines interact with the vascular endothelium, resulting in activation and nuclear accumulation of the nuclear transcription factor, nuclear factor kappa B (NFkappaB). In turn, NFkappaB transactivates relevant proinflammatory genes, resulting in an amplification of the inflammatory response....
Article
In vitro studies have indicated that polymorphonuclear leukocytes (PMNs) traverse endothelial cell monolayers via the paracellular pathway (i.e., through endothelial cell-cell junctions. Herein, we assessed whether the adherens junctions (AJs) are disrupted during PMN transendothelial cell migration. Human umbilical vein endothelial cells (HUVECs)...
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Full-text available
Activating protein (AP-1) transcription factors participate in the regula-tion of different target genes and thus execute distinct biological func-tions such as cell proliferation, differentiation and apoptosis. The pre-sent study examined the influence of post-translational modifications (phosphorylation, acetylation, glycosylation) on the activat...
Article
Full-text available
The relationship between RA- or dbcaMP-mediated differentiation and subsequent apoptosis in HL-60 cells was assessed by modulating the levels of differentiation suppressing the activity of PKC and PKA with calphostin C or GF 109203X and H89, respectively. Results demonstrated that (1) RA and dbcAMP caused a dose-dependent increase in apoptosis conc...
Article
Full-text available
The two-dimensional electrophoretic patterns of nuclear proteins and their tyrosine phosphorylation were compared for HL-60 cells before and after differentiation induction to granulocytes by dimethyl sulfoxide, all-trans retinoic acid and N 6,O 2-dibutyryl adenosine 3′5′-cyclic monophosphate. Regardless of the inducer used, some nuclear proteins,...
Article
Full-text available
The influence of protein kinases on the differentiation of a human promyelocytic leukemia-cell line HL-60 to granulocytes was studied by using H8 and staurosporine as inhibitors of PKA and PKC respectively. In order to determine the significance of these protein kinases of uninduced and differentiating cells for the final differentiation, the cells...
Article
The human promyelocytic leukemia cell line HL-60 was induced to differentiate to mature granulocytic cells by dbcAMP or RA. The influence of distinct protein kinases during different stages of this differentiation was studied by the use of H8, staurosporine and genistein as inhibitors of PKA, PKC and PTK respectively. In dbcAMP-mediated differentia...
Article
Full-text available
Leukemogenesis is controlled by a number of transcription factors regu-lating the expression of essential genes, including human neutrophil elas-tase (HNE). Herein, we have investigated activity of the transcription factor PU.1 as a major regulator of myeloid development in association with modulated cell differentiation by protein kinase inhibitor...
Article
Full-text available
Glycoproteins are classically regarded as components of the plasma membrane and extracellular spaces. The notion that glycoproteins occur in the nuclear and/or cytoplasmic portions of the cell has only recently gained wide acceptance. The studies reported here were designated to evaluate the effect of tunicamycin (Tu) and isopropylthiogalactoside (...
Article
Full-text available
It was shown that all-trans retinoic acid and its isomer 9-cis retinoic acid inhibit the proliferation and induce differentiation of promyelocytic cell line HL-60 and leukemic cells from patients with acute promyelocytic leukemia. Retinoic acid receptors and retinoid X receptors act as ligand-inducible transc-ription factors – bind to specific DNA...
Article
Full-text available
Our research is concentrated on identification of newly synthesized and/ or modified nuclear proteins during HL-60 cell differentiation. These proteins can be involved in cell differentiation signaling or can be res-ponsible for reorganization of the nucleus at the maturation stage of HL-60 cells. The HL-60 human promyelocytic leukemia cell line wa...
Article
Full-text available
The nuclear factor κB (NFκB) is one of the important transcriptional regulatory proteins interacting with many genes and has been implicated in cellular programs such as growth and differentiation. The present study examines the influence of post-translational modifications (phosphoryla-tion, acetylation, glycosylation) on activation of the NFκB du...

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