scholarly journals Photocytotoxic Activity of Ruthenium(II) Complexes with Phenanthroline-Hydrazone Ligands

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2084
Author(s):  
Priscila Pereira Silva-Caldeira ◽  
Antônio Carlos Almendagna de Oliveira Junior ◽  
Elene Cristina Pereira-Maia
Keyword(s):  
Anticancer Agents ◽  
Metal Ion ◽  
Uv Light ◽  
Light Exposure ◽  
Leukemia Cell ◽  
Acid Hydrazide ◽  
Cellular Growth ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line ◽  
Chronic Myelogenous Leukemia Cell

This paper reports on the synthesis and characterization of two new polypyridyl-hydrazone Schiff bases, (E)-N′-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)thiophene-2-carbohydrazide (L1) and (E)-N′-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)furan-2-carbohydrazide (L2), and their two Ru(II) complexes of the general formula [RuCl(DMSO)(phen)(Ln)](PF6). Considering that hydrazides are a structural part of severa l drugs and metal complexes containing phenanthroline derivatives are known to interact with DNA and to exhibit antitumor activity, more potent anticancer agents can be obtained by covalently linking the thiophene acid hydrazide or the furoic acid hydrazide to a 1,10-phenanthroline moiety. These ligands and the Ru(II) complexes were characterized by elemental analyses, electronic, vibrational, 1H NMR, and ESI-MS spectroscopies. Ru is bound to two different N-heterocyclic ligands. One chloride and one S-bonded DMSO in cis-configuration to each other complete the octahedral coordination sphere around the metal ion. The ligands are very effective in inhibiting cellular growth in a chronic myelogenous leukemia cell line, K562. Both complexes are able to interact with DNA and present moderate cytotoxic activity, but 5 min of UV-light exposure increases cytotoxicity by three times.

scholarly journals Expression of c-jun during macrophage differentiation of HL-60 cells

Blood ◽  
1991 ◽  
Vol 77 (12) ◽  
pp. 2618-2623 ◽  
Author(s):  
R Gaynor ◽  
K Simon ◽  
P Koeffler
Keyword(s):  
Leukemia Cell ◽  
Early Response ◽  
Cellular Growth ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line ◽  
Northern Analysis ◽  
Macrophage Differentiation ◽  
Cellular Transcription Factor ◽  
Cellular Genes ◽  
Cellular Transcription

Abstract Cellular transcription factors are important in the regulation of cellular genes. Recent studies have indicated that a class of cellular genes known as early response genes are important in the control of cellular growth properties. Two of these genes, c-jun and c-fos, play an important role in the control of cellular differentiation. Because the acute myelogenous leukemia cell line, HL-60, is capable of differentiating to either macrophages or granulocytes, it provides a good model to understand differential gene expression. To determine if the modulation of c-jun was important in the differentiation of HL-60 cells to either macrophages or granulocytes, expression of c-jun mRNA was determined by Northern analysis at various times following treatment with a variety of differentiating agents, including 12- tetradeconyl-phorbol 13-acetate (TPA), retinoic acid (RA), dimethyl sulfoxide (DMSO), or 1,25 dihydroxyvitamin D3 [1,25 (OH)2 D3]. Both TPA and 1,25(OH)2D3, which induce HL-60 cells to differentiate to macrophages, resulted in marked increases in c-jun mRNA; while RA and DMSO, which induce HL-60 cells to differentiate to granulocytes, did not greatly alter c-jun mRNA expression. HL-60 cell lines resistant to macrophage differentiation after exposure to either 1,25(OH)2D3 or TPA did not result in increases in c-jun mRNA. These results suggest that elevation of c-jun mRNA in HL-60 cells correlated temporally with differentiation to macrophages. Thus, c-jun may be a critical cellular transcription factor involved in macrophage differentiation.

scholarly journals Dye-mediated photolysis is capable of eliminating drug-resistant (MDR+) tumor cells

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 793-800 ◽  
Author(s):  
RM Lemoli ◽  
T Igarashi ◽  
M Knizewski ◽  
L Acaba ◽  
A Richter ◽  
...  
Keyword(s):  
Cell Line ◽  
Tumor Cells ◽  
Cell Lines ◽  
Light Exposure ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line ◽  
Drug Resistant ◽  
Colony Forming Unit

Abstract We evaluated the potential role of photoradiation therapy with a benzoporphyrin derivative, monoacid ring A (BPD-MA), and dihematoporphyrin ether (DHE), for the ex vivo purging of residual tumor cells from autologous bone marrow (BM) grafts. BPD-MA and DHE photosensitizing activity was tested against two human large-cell lymphoma cell lines and colony-forming unit-leukemia (CFU-L) derived from patients with acute myelogenous leukemia (AML). In mixing experiments, 4-log elimination of tumor cell lines was observed after 1 hour of incubation with 75 ng/mL of BPD-MA or 30 minutes of treatment with 12.5 micrograms/mL of DHE followed by white light exposure. By comparison, using the same concentration of BPD-MA, the mean recovery of normal BM progenitors was 4% +/- 0.8% (mean +/- SD) for granulocyte- macrophage colony-forming unit (CFU-GM) and 5% +/- 0.8% for burst- forming unit-erythroid (BFU-E). Similarly, DHE treatment resulted in the recovery of 5.2% +/- 2% and 9.8% +/- 3% of CFU-GM and BFU-E, respectively. Furthermore, equivalently cytotoxic concentrations of both DHE and BPD-MA and light were found not to kill normal pluripotent stem cells in BM, as demonstrated by their survival in two-step long- term marrow culture at levels equal to untreated controls. The T- lymphoblastic leukemia cell line CEM and its vinblastine (VBL)- resistant subline CEM/VBL, along with the acute promyelocyte leukemia cell line HL-60 and its vincristine (VCR)-resistant subline HL-60/VCR, were also tested. BPD-MA at 75 ng/mL was able to provide a greater than 4-log elimination of the drug-sensitive cell lines, but only a 34% and 55% decrease of the drug-resistant HL-60/VCR and CEM/VBL cell lines, respectively. On the contrary, 12.5 micrograms/mL of DHE reduced the clonogenic growth of all the cell lines by more than 4 logs. Further experiments demonstrated decreased uptake of both BPD-MA and DHE by the resistant cell lines. However, all the cell lines took up more DHE than BPD-MA under similar experimental conditions. Our results demonstrate the preferential cytotoxicity of BPD-MA and DHE toward neoplastic cell lines and CFU-L from AML patients. In addition, DHE was slightly more effective in purging tumor cells expressing the p-170 glycoprotein. These results suggest that photoradiation with DHE would be useful for in vitro purging of residual drug-resistant leukemia and lymphoma cells.

Analysis of Histone Deacetylase Inhibitor, FK228, Effect on Chronic Myelogenous Leukemia Cell Line.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4675-4675
Author(s):  
Seiichi Okabe ◽  
Testuzo Tauchi ◽  
Akihiro Nakajima ◽  
Goro Sashida ◽  
Masahiki Sumi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Clinical Trial ◽  
Cell Line ◽  
Chronic Myelogenous Leukemia ◽  
Glycogen Synthase ◽  
Leukemia Cell ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line ◽  
Parental Cell Line ◽  
Chronic Myelogenous Leukemia Cell

Abstract Chronic myelogenous leukemia (CML) results from transformation of hematopoietic cells by the BCR/ABL gene. Although high rates of hematologic responses to imatinib therapy, the acquired resistance to imatinib has been recognized as a major problem in the treatment of CML Histone deacetylases (HDACs) and histone acetyltransferases (HATs) regulate gene expression and cell growth. Recently, HDAC inhibitors have known as a new class of anti-cancer drugs. One of the HDAC inhibitor, FK228 (FR901228, depsipeptide) is now doing the clinical trial for the treatment of patients, such as peripheral T-cell lymphoma, but there was not known to the CML. In this study, we used the TF-1 BCR-ABL cell line, which were transfected BCR/ABL gene to the leukemia cell line, TF-1. We show here that FK228 potently induced apoptosis of TF-1 BCR-ABL cells, compare to the parental cell line, TF-1, in a dose and time depend fashion. BCR-ABL, intracellular molecular chaperone, heat shock protein 90 (HSP90), and p53 which regulate cell cycle, were acetylated after FK228 treatment, but not glycogen synthase kinase-3 β(GSK-3β) and signal-transducing activators of transcription 5 (STAT5). Histone H4 is also acetylated after FK228 treatment. In a cell cycle analysis, TF-1 BCR-ABL cells were stopped at G2-M phase after FK228 treatment. The activity of MAPK and Src kinases were blocked after FK228 treatment in a time and dose depend fashion, but p38 was activated. Inhibitor of apoptosis proteins (c-IAPs) have prevented cell death by inhibiting effectors caspases. IAPs were inhibited by FK228 and caspase3, caspase9 and poly (ADP-ribose) polymerase (PARP) were activated in a time and dose depend manner. Histone acetylation and caspase activitation were not blocked by treatment of p38 inhibitor, SB203580. Our study supports the future clinical trial of FK228 in the management of CML patients.

scholarly journals Induction of erythropoietic colonies in a human chronic myelogenous leukemia cell line

Blood ◽  
1979 ◽  
Vol 54 (5) ◽  
pp. 1182-1187 ◽  
Author(s):  
R Hoffman ◽  
MJ Murnane ◽  
EJ Jr Benz ◽  
R Prohaska ◽  
V Floyd ◽  
...  
Keyword(s):  
Cell Line ◽  
Chronic Myelogenous Leukemia ◽  
Sodium Butyrate ◽  
K562 Cell ◽  
Leukemia Cell ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line ◽  
Erythroid Cell ◽  
K562 Cell Line ◽  
Chronic Myelogenous Leukemia Cell

The ability of cells derived from the K562 cell line to generate erythropoietic colonies was studied. The K562 cell line was derived from a patient with chronic myelogenous leukemia 8 yr ago by Lozzio and Lozzio. Rare benzidine-positive colonies formed when these cells were cloned in plasma clots (3 +/- 1/10(4) cells), and their number was not substantially increased by the addition of erythropoietin (9.5 +/- 1/10(4) cells). Sodium butyrate was capable of markedly enhancing the number of benzidine-positive colonies (19.5 +/- 1/10(4) cells) formed, while the combination of sodium butyrate plus erythropoietin exerted a synergistic effect on erythropoietic colony formation (57 +/- 4/10(4) cells). The K562 cell line is a long-term culture system that contains human erythropoietic stem cells. This cell line should be useful in future studies on the cellular and molecular events associated with human erythroid cell differentiation.

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