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Archives of Biochemistry and Biophysics Mar 2019Isoniazid (INH) is one of the oldest drugs for the treatment of tuberculosis (TB) and is of continual clinical and research interest. The aim of the current study is to...
Isoniazid (INH) is one of the oldest drugs for the treatment of tuberculosis (TB) and is of continual clinical and research interest. The aim of the current study is to investigate the ability of INH to induce monocyte differentiation and the underlying signaling pathway involved in this phenomenon using HL-60 cells. In this study, HL-60 cells were treated with different non-cytotoxic concentrations of INH or vitamin D (a well-known inducer of monocytic differentiation) to determine key functional changes in the phenotype of these cells using several biochemical and cytobiological experiments. HL-60 cells are derived from human promyelocytic leukemia and bear some resemblance to promyelocytes, which differentiate into various cell types. INH-induced differentiation was confirmed to occur in a concentration-dependent manner through several functional markers such as nonspecific esterase activity, NADPH oxidase activity and expression of surface markers CD14 and CD16 (characteristic of monocytes). INH-induced monocytic-like differentiation in HL-60 cells and demonstrated that at least 25% of cells were differentiated within the range of the pharmacological concentrations of INH. To determine the effects of INH on HL-60 cells, we applied quantitative proteomics that revealed 32 proteins were altered significantly in pathways that could involve differentiation signals. Lastly, INH activated the ERK-1/MAPK signaling pathway based on detection of phosphorylated ERK-1. These in vitro findings in HL-60 cells warrant further study using promyelocytes or hematopoietic stem cells to evaluate the physiological capability of INH to induce monocytic differentiation that may aid in host defense against TB.
Topics: Cell Survival; Gene Expression Regulation; HL-60 Cells; Humans; Isoniazid; Lipopolysaccharide Receptors; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 3; Monocytes; NADPH Oxidases; Phenotype; Receptors, IgG
PubMed: 30682330
DOI: 10.1016/j.abb.2019.01.004 -
Journal of Natural Products Jul 2020Five new drimane-type sesquiterpenoids, named proversilins A-E (-), were isolated from the endophytic fungus F210 isolated from the bulbs of . Their structures and...
Five new drimane-type sesquiterpenoids, named proversilins A-E (-), were isolated from the endophytic fungus F210 isolated from the bulbs of . Their structures and absolute configurations were characterized by extensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS data, comparison of experimental and calculated electronic circular dichroism data, and X-ray crystallography. Proversilins B-E (-) represent the first examples of natural products featuring an -acetyl-β-phenylalanine moiety. Compounds and inhibited the growth of HL-60 cells with IC values of 7.3 and 9.9 μM, respectively.
Topics: Aspergillus; Crystallography, X-Ray; HL-60 Cells; Humans; Molecular Structure; Sesquiterpenes; Spectrum Analysis
PubMed: 32628478
DOI: 10.1021/acs.jnatprod.0c00298 -
Fundamental & Clinical Pharmacology Jun 2023Chemotherapy with targeted drugs is the first line therapy option for acute and chronic myeloid leukemia. However, hematopoietic stem cell transplantation may be used in...
Chemotherapy with targeted drugs is the first line therapy option for acute and chronic myeloid leukemia. However, hematopoietic stem cell transplantation may be used in high-risk patients or patients with failed responses to chemo drugs. Discovery and development of more effective new agents with lower side effects is the main aim of leukemia treatment. In this study, a novel retinoid compound with tetrahydronaphthalene ring was synthesized and evaluated for anticancer activity in human chronic and acute myeloid leukemia cell lines K562 and HL-60. Novel N-(1H-indol-1-yl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carboxamide was synthesized based on molecular hybridization of the two different bioactive structures retinoid head and indole. The effects of the synthesized carboxamide compound, which was referred to as compound 5, were determined in K562 chronic myeloid leukemia and HL-60 acute myeloid leukemia cell lines and L929 fibroblast cell line, which served as a control. Colorimetric MTT and caspase3 activity tests, flow cytometry, western blot, and microscopic examinations were used to evaluate biological activity. Compound 5 more effectively induced cell death in HL60 cells in comparison to K562 cells and L929 fibroblast cells. Therefore, further mechanism of cell death was investigated in HL60 cell line. It was found that compound 5 induced remarkable cytotoxicity, caspase3 activation, and PARP fragmentation in HL60 cells. Flow cytometric staining showed that the percentage of cells arrested in G0/G1 was also increased with compound 5 treatment. Important modulator proteins of cell proliferation p-ERK, p-AKT, and p-m-TOR were also found to be inhibited with compound 5 treatment. Collectively, our results reveal compound 5, which is a novel indole retinoid compound as a potential active agent for the treatment of acute promyelocytic leukemia.
Topics: Humans; HL-60 Cells; Proto-Oncogene Proteins c-akt; Retinoids; Apoptosis; Cell Cycle Checkpoints; Cell Proliferation; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Indoles; Tetrahydronaphthalenes
PubMed: 36690337
DOI: 10.1111/fcp.12876 -
BMJ Case Reports Jan 2024Myeloid sarcoma is a very rare extramedullary malignant tumour, most often associated with acute myeloid leukaemia. We report the case of a man in his early 20s who...
Myeloid sarcoma is a very rare extramedullary malignant tumour, most often associated with acute myeloid leukaemia. We report the case of a man in his early 20s who presented with chronic headache, raised intracranial pressure and progressive vision loss of 2 years duration with no systemic manifestations. He had a history of myeloid sarcoma of the left thigh 15 years ago, treated with external beam radiotherapy and in complete remission for more than 13 years. However, the progressive blindness remained unexplained for 2 years, and he was eventually diagnosed with isolated meningeal relapse without marrow or systemic involvement. Imaging revealed subarachnoid haemorrhage, diffuse leptomeningeal enhancement and involvement of lower dorsal cord and conus, and cerebrospinal fluid cytology showed myeloid blasts. He was managed with intrathecal chemotherapy and craniospinal irradiation, after which he had mild improvement in vision.
Topics: Male; Humans; Sarcoma, Myeloid; Neoplasm Recurrence, Local; Meningeal Neoplasms; Blindness; Granulocyte Precursor Cells
PubMed: 38191225
DOI: 10.1136/bcr-2023-256821 -
Anticancer Research Apr 2022As part of our continuing investigation in coumarin derivatives as potential anticancer substances, a series of alkylpsoralens were synthesized, and their...
BACKGROUND/AIM
As part of our continuing investigation in coumarin derivatives as potential anticancer substances, a series of alkylpsoralens were synthesized, and their antiproliferative activity was evaluated in leukemic HL60 cells.
MATERIALS AND METHODS
Alkylpsoralens were systematically synthesized from the combination of several chloroketones and 7-hydroxycoumarin derivatives.
RESULTS
Among the compounds synthesized, 4,4',8-trimethylpsoralen demonstrated the most potent activity (IC=6.6 μM).
CONCLUSION
The correlation between the alkylation pattern and antiproliferative activity showed the importance of the C4-methyl and C8-methyl moieties in the psoralen nucleus as well as the importance of lipophilicity for their antiproliferative activity.
Topics: Antineoplastic Agents; Coumarins; HL-60 Cells; Humans
PubMed: 35346996
DOI: 10.21873/anticanres.15654 -
European Review For Medical and... Mar 2019MAPK kinase 1 (MEK1), also known as MAP2K1, plays a role in activating extra-cellular signal-regulated protein kinase/mitogen-activated protein kinase (ERK/MAPK)...
OBJECTIVE
MAPK kinase 1 (MEK1), also known as MAP2K1, plays a role in activating extra-cellular signal-regulated protein kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway to regulate cell proliferation and apoptosis. The abnormal expression of MAP2K1 is associated with leukemia. Bioinformatics analysis showed the targeted relationship between microRNA-181a (miR-181a) and the 3'-UTR of MAP2K1. This study aimed to investigate the role of miR-181a in regulating MAP2K1 expression, the effects on leukemic cell proliferation, apoptosis, and adriamycin (ADM) resistance.
MATERIALS AND METHODS
Dual luciferase reporter gene assay was applied to confirm the targeted relationship between miR-181a and MAP2K1. ADM resistant cell line HL-60/ADM was established. MiR-181a and MAP2K1 expressions were detected. HL-60/ADM cells were cultured in vitro and divided into two groups, including microRNA-Normal control (miR-NC) group and miR-181a mimic group. MAP2K1, phosphorylated MAP2K1 (p-MAP2K1), and phosphorylated ERK (p-ERK) protein expressions were tested. Cell apoptosis was assessed with flow cytometry. Cell proliferation was determined using EdU staining.
RESULTS
There is a targeted regulatory relationship between miR-181a and MAP2K1 mRNA. miR-181a expression was significantly lower, while MAP2K1 mRNA and protein expressions were markedly higher in HL-60/ADM cells than HL-60 cells (p<0.05). Transfection of miR-181a mimic markedly reduced expressions of MAP2K1, p-MAP2K1, and p-ERK in HL-60/ADM cells, enhanced cell apoptosis, and weakened cell proliferation compared to miR-NC (p<0.05).
CONCLUSIONS
MiR-181a reduction and MAP2K1 elevation were related to ADM resistance in leukemia cells. Up-regulation of miR-181a expression inhibited leukemia cell proliferation, induced apoptosis, and reduced ADM resistance via targeting MAP2K1 expression and ERK/MAPK signaling pathway.
Topics: 3' Untranslated Regions; Cell Proliferation; Cell Survival; Down-Regulation; Doxorubicin; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; HL-60 Cells; Humans; Leukemia, Promyelocytic, Acute; MAP Kinase Kinase 1; MicroRNAs
PubMed: 30964176
DOI: 10.26355/eurrev_201903_17397 -
Journal of Natural Products Feb 2022Harringtonine (HT), produced from species, is known to exhibit potent antiproliferative activity against myeloid leukemia cells by inhibiting protein synthesis. A...
Harringtonine (HT), produced from species, is known to exhibit potent antiproliferative activity against myeloid leukemia cells by inhibiting protein synthesis. A previous study using acute promyelocytic leukemia (HL-60) cells raised the possibility that the C-5' methyl group of HT plays an important role in regulating leukemia cell line antiproliferative activity. In order to investigate the effect of hydrocarbon chains at C-5' on the resultant activity, the C-5' methyl group was replaced with various straight- and branched-chain hydrocarbons using the corresponding alcohols, and their antiproliferative activity against HL-60 and HeLa cells was investigated. As a result, 4'--heptyl-4'-demethylharringtonine (, -heptyl derivative) showed the most potent cytotoxicity among the HT ester derivatives produced, with IC values of 9.4 nM and 0.4 μM for HL-60 and HeLa cells, respectively. Interestingly, the cytotoxicity of derivative against HL-60 and HeLa cells respectively was ∼5 (IC = 50.5 nM) and ∼10 times (IC = 4.0 μM) those of HT and ∼2 (IC = 21.8 nM) and ∼4 times (IC = 1.7 μM) more than homoharringtonine (HHT). These results demonstrate the potential of the derivative as a lead compound against leukemia.
Topics: Esters; HL-60 Cells; Harringtonines; HeLa Cells; Humans; Leukemia, Promyelocytic, Acute
PubMed: 35148094
DOI: 10.1021/acs.jnatprod.1c00888 -
Biomeditsinskaia Khimiia Dec 2023Plasma membrane proteins with extracellular-exposed domains are responsible for transduction of extracellular signals into intracellular responses, and their...
Plasma membrane proteins with extracellular-exposed domains are responsible for transduction of extracellular signals into intracellular responses, and their accessibility to therapeutic molecules makes them attractive targets for drug development. In this work, using omics technologies and immunochemical methods, we have studied changes in the content of markers of clusters of differentiation (CD markers) of neutrophils (CD33, CD97, CD54, CD38, CD18, CD11b, CD44, and CD71) at the level of transcripts and proteins in NB4, HL-60 and K562 cell lines, induced by the treatment with all-trans-retinoic acid (ATRA). Transcriptomic analysis revealed the induction of CD38, CD54, CD11b, and CD18 markers as early as 3 h after the addition of the inducer in the ATRA-responsive cell lines HL-60 and NB4. After 24 h, a line-specific expression pattern of CD markers could be observed in all cell lines. Studies of changes in the content of CD antigens by means of flow cytometry and targeted mass spectrometry (MS) gave similar results. The proteomic profile of the surface markers (CD38, CD54, CD11b, and CD18), characteristic of the NB4 and HL-60 lines, reflects different molecular pathways for the implementation of ATRA-induced differentiation of leukemic cells into mature neutrophils.
Topics: Humans; Leukemia, Promyelocytic, Acute; Proteomics; Tretinoin; HL-60 Cells; Cell Differentiation
PubMed: 38153053
DOI: 10.18097/PBMC20236906383 -
Biomolecules Oct 2022Autophagy is a fundamental catabolic process of cellular survival. The role of autophagy in cancer is highly complex: in the early stages of neoplastic transformation,...
Autophagy is a fundamental catabolic process of cellular survival. The role of autophagy in cancer is highly complex: in the early stages of neoplastic transformation, it can act as a tumor suppressor avoiding the accumulation of proteins, damaged organelles, and reactive oxygen species (ROS), while during the advanced stages of cancer, autophagy is exploited by cancer cells to survive under starvation. 6-(Methylsulfonyl) hexyl isothiocyanate (6-MITC) is the most interesting compound in the rizhome. Recently, we proved its ability to induce cytotoxic, cytostatic, and cell differentiation effects on leukemic cell lines and its antimutagenic activity on TK6 cells. In the current study, to further define its chemopreventive profile, Jurkat and HL-60 cells were treated with 6-MITC for 24 h. The modulation of the autophagic process and the involvement of ROS levels as a possible trigger mechanisms were analyzed by flow cytometry. We found that 6-MITC induced autophagy in Jurkat and HL-60 cells at the highest concentration tested and increased ROS intracellular levels in a dose-dependent manner. Our results implement available data to support 6-MITC as an attractive potential chemopreventive agent.
Topics: Humans; Reactive Oxygen Species; Cytostatic Agents; Isothiocyanates; Leukemia; Autophagy; HL-60 Cells; Apoptosis; Cell Line, Tumor
PubMed: 36291694
DOI: 10.3390/biom12101485 -
Journal of Visualized Experiments : JoVE Apr 2019A key aspect of the immune response to bacterial colonization of the host is phagocytosis. An opsonophagocytic killing assay (OPKA) is an experimental procedure in which...
A key aspect of the immune response to bacterial colonization of the host is phagocytosis. An opsonophagocytic killing assay (OPKA) is an experimental procedure in which phagocytic cells are co-cultured with bacterial units. The immune cells will phagocytose and kill the bacterial cultures in a complement-dependent manner. The efficiency of the immune-mediated cell killing is dependent on a number of factors and can be used to determine how different bacterial cultures compare with regard to resistance to cell death. In this way, the efficacy of potential immune-based therapeutics can be assessed against specific bacterial strains and/or serotypes. In this protocol, we describe a simplified OPKA that utilizes basic culture conditions and cell counting to determine bacterial cell viability after co-culture with treatment conditions and HL-60 immune cells. This method has been successfully utilized with a number of different pneumococcal serotypes, capsular and acapsular strains, and other bacterial species. The advantages of this OPKA protocol are its simplicity, versatility (as this assay is not limited to antibody treatments as opsonins), and minimization of time and reagents to assess basic experimental groups.
Topics: Bacteria; Biological Assay; Cell Survival; HL-60 Cells; Humans; Opsonin Proteins; Phagocytosis
PubMed: 31009013
DOI: 10.3791/59400