scholarly journals A comparative experiment on the anti-chronic myeloid leukemia capacities of AgNO3, ‎Scrophularia striata leaf aqueous extract, and silver nanoparticles containing natural ‎compounds ‎

2022 ◽  
Author(s):  
Yanmei Ma ◽  
Maryam Behtash ◽  
Hadis Yari ◽  
Mohammad Karimian ◽  
Naser Abbasi ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Silver Nanoparticles ◽  
Chronic Myeloid Leukemia ◽  
Cell Line ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Butylated Hydroxytoluene ◽  
Ft Ir ◽  
Scrophularia Striata

IntroductionIn the current study, silver nanoparticles were prepared and synthesized in aqueous medium using Scrophularia ‎striata leaf extract as stabilizing and reducing agents. Also, we investigated the anti-chronic myeloid leukemia ‎potentials of silver nanoparticles against BV173 (chronic myeloid leukemia in blast crisis), CML-T1 (chronic ‎myeloid leukemia in lymphoid blast crisis), EM-2 (chronic myeloid leukemia in blast crisis; relapse after bone ‎marrow transplantation), and JOSK-M (chronic myeloid leukemia in myelomonocytic) cell lines. ‎Material and methodsSilver nanoparticles were characterized and analyzed using common nanotechnology techniques including UV-‎Vis.‎‏ ‏and FT-IR Spectroscopy, Field Emission-Scanning Electron Microscopy (FE-SEM), and Transmission ‎Electron Microscopy (TEM), and Energy Dispersive X‐ray Spectrometry (EDS). ‎ResultsFT-IR analysis offered antioxidant compounds in the nanoparticles were the sources of reducing power, ‎reducing silver ions to silver nanoparticles. FE-SEM and TEM images revealed a uniform spherical morphology ‎in size of 19.72 nm for the green synthesized nanoparticles. DPPH test revealed similar antioxidant potentials ‎for silver nanoparticles and butylated hydroxytoluene. Silver nanoparticles had very low cell viability and anti-‎chronic myeloid leukemia properties dose-dependently against JOSK-M, EM-2, CML-T1, and BV173 cell lines ‎without any cytotoxicity on the HUVEC cell line. The best result of cytotoxicity properties of silver ‎nanoparticles against the above cell lines was observed in the case of CML-T1 cell line. ‎ConclusionsAfter confirming in the in vivo and clinical trial studies, these nanoparticles can be administrated in humans for ‎the treatment of chronic myeloid leukemia.‎

Restoration of sensitivity to STI571 in STI571-resistant chronic myeloid leukemia cells

Blood ◽  
2001 ◽  
Vol 98 (13) ◽  
pp. 3864-3867 ◽  
Author(s):  
Alex J. Tipping ◽  
François X. Mahon ◽  
Valerie Lagarde ◽  
John M. Goldman ◽  
Junia V. Melo
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Cell Line ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Leukemia Cells ◽  
Sharp Reduction ◽  
Resistant Lines ◽  
Resistant Cells

Abstract STI571 induces sustained hematologic remission in patients with chronic myeloid leukemia (CML) in chronic phase. However, in advanced phases, especially blast crisis, the leukemia usually becomes resistant within months. It has been investigated whether resistance to STI571 is stable and immutable or whether it can be reversed in selected CML cell lines. Withdrawal of STI571 for varying lengths of time from cultures of 3 resistant lines (K562-r, KCL22-r, and Baf/BCR-ABL–r1) did not restore sensitivity to the inhibitor. In contrast, LAMA84-resistant cells experienced a sharp reduction in survival and proliferation during the first week of STI571 withdrawal but recovered thereafter. Moreover, when left off the inhibitor for 2 months or longer, this cell line reacquired sensitivity to STI571. It is hypothesized, therefore, that patients who have become resistant to the drug may respond again if STI571 therapy is temporarily interrupted.

RIZ1 Tumor Suppressor Regulates IGF-1 Autocrine Loop To Control Cell Proliferation, Apoptosis, and Differentiation in Chronic Myeloid Leukemia Blast Crisis Cell Lines.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1208-1208
Author(s):  
Naoto Takahashi ◽  
Wei-Feng Dong ◽  
Matthew Bainbridge ◽  
Andrea Hull ◽  
Elodie Pastural ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Chronic Myeloid Leukemia ◽  
Tumor Suppressor ◽  
Cell Line ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Histone H3 ◽  
K562 Cells ◽  
Number Of Cells

Abstract RIZ1 (PRDM2) is a tumor suppressor gene whose expression and activity are reduced by genetic and epigenetic aberrations in many cancers. In chronic myeloid leukemia (CML), blastic transformation is associated with loss of heterozygosity at 1p36, the region where RIZ1 is located, suggesting that RIZ1 has an essential role in CML pathogenesis. In CML patients and in the CML blast crisis cell line K562, we observed aberrant RIZ1 promoter methylation. To further characterize RIZ1 tumor suppressor properties that are related to CML, we analyzed RIZ1-induced changes in proliferation, apoptosis, and differentiation in CML myeloid blast crisis (CML-BC) cell lines (K562, ERY-1, YN-1, and JURL-MK1) that express low levels of endogenous RIZ1. Forced RIZ1 expression in CML-BC cell lines substantially decreased proliferation, increased apoptosis, and increased the population of cells in G2/M phase of the cell cycle. RIZ1 expression also promoted differentiation as assessed by benzidine staining in CML-BC cell lines expressing immature erythroid cell features (K562, ERY-1, YN-1) and by CD117 and CD33 expression in JURL-MK1, a CML-BC cell line expressing megakaryoblastic features. To identify genes and pathways influenced by RIZ1 expression, we used 42k cDNA microarrays to globally monitor how RIZ1 expression changes the gene expression profile of K562 cells. We discovered 25 RIZ1-regulated genes that are involved in a variety of biological processes with a subgroup of genes involved in IGF-1 signaling. The most strongly RIZ1 down-regulated genes (IGF1) and up-regulated genes (SPARC, IGFBP2) are involved in IGF-1 signaling. Using chromatin immunoprecipitation (ChIP), we determined that RIZ1 associates with IGF-1 and SPARC promoters. RIZ1 contains a PR domain that has Histone H3 lysine 9 methylation activity, which is implicated in gene repression. Using ChIP assays, we found that RIZ1 expression in K562 cells increased Histone H3 lysine 9 methylation of the IGF-1 promoter. The increased Histone H3 lysine 9 methylation is associated with decreased IGF-1 expression as monitored by RT-PCR and Western analysis. We observed autocrine production of IGF-1 in K562 cells, by culturing cells in serum free media and monitoring IGF-1 production and signaling. We detected receptor bound IGF-1 by flow cytometry, and compared the growth properties of sorted IGF-1 positive and negative cells. IGF-1 positive cells have increased number of cells in G2/M and S phase, a reduced number of cells in G1 and higher numbers of mitoses and Ki-67 positive nuclei compared with IGF-1 negative cells. RIZ1 expression in K562 decreased the amount of receptor bound IGF-1, reduced IGF-1 receptor activation, and reduced the activity of downstream IGF-1 signaling pathways. RIZ1 expression in K562 substantially reduced AKT1 and ERK1/2 phosphorylation. Our study demonstrates that RIZ1 reduces cell proliferation, increases apoptosis, and enhances differentiation of CML blast crisis cell lines. RIZ1 also controls autocrine production of IGF-1 and blocks the activity of IGF-1 signaling pathways. These activities may in part be responsible for RIZ1 tumor suppressor activity and point to the therapeutic potential of IGF-1 pathway inhibition in the acute phase of CML.

scholarly journals Formulation of a novel anti-human bone tumor supplement by silver nanoparticles green-synthesized using Nigella sativa leaf aqueous extract

2021 ◽  
Author(s):  
Yijiang Huang ◽  
Ruimin Xu ◽  
Pei Fan ◽  
Liang Chen ◽  
Daosen Chen ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Silver Nanoparticles ◽  
Cell Line ◽  
Cell Lines ◽  
Aqueous Extract ◽  
Bone Tumor ◽  
Nigella Sativa ◽  
Human Bone ◽  
Butylated Hydroxytoluene ◽  
Dpph Test

IntroductionIn the present research, we formulated a modern chemotherapeutic drug by silver nanoparticles (AgNPs) containing Nigella sativa aqueous extract for the treatment of bone tumor.Material and methodsCharacterization of AgNPs was done by UV–Visible Spectroscopy (UV-Vis), Fourier Transformed Infrared Spectroscopy (FT‐IR), Transmission Electron Microscopy (TEM), and Field Emission Scanning Electron Microscopy (FE‐SEM). For investigating the antioxidant properties of AgNO3, N. sativa, and AgNPs, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. To survey the cytotoxicity and anti-bone tumor effects of AgNO3, N. sativa, and AgNPs, MTT assay was used on the human bone Ewing’s sarcoma (CADO-ES1 and MHH-ES1), human bone osteosarcoma (HOS and MG-63), and human bone chondrosarcoma (SW-1353 and CH-3573) cell lines.ResultsDPPH test revealed similar antioxidant potentials for N. sativa, AgNPs, and butylated hydroxytoluene. Silver nanoparticles had very low cell viability and anti-bone tumor properties dose-dependently against CADO-ES1, MHH-ES1, HOS, MG-63, SW-1353, and CH-3573 cell lines without any cytotoxicity on the normal cell line. The best result of anti-bone tumor properties of AgNPs against the above cell lines was seen in the case of the MG-63 cell line.ConclusionsAccording to the above findings, the silver nanoparticles containing N. sativa aqueous extract can be administrated in humans for the treatment of several types of bone tumors.

scholarly journals Preparation, characterization and investigation of the anti-‎human ovarian cancer of silver nanoparticles green-formulated by Salvia officinalis leaf ‎aqueous extract ‎

2022 ◽  
Author(s):  
Danxia Luo ‎ ◽  
Arunachalam Chinnathambi ◽  
Tahani Awad Alahmadi ◽  
Prabakaran D.S. ◽  
Gaofeng Zhang
Keyword(s):  
Ovarian Cancer ◽  
Silver Nanoparticles ◽  
Cell Line ◽  
Cell Lines ◽  
Aqueous Extract ◽  
Salvia Officinalis ◽  
Butylated Hydroxytoluene ◽  
Human Ovarian Cancer ◽  
Leaf Aqueous Extract ◽  
Ft Ir

IntroductionIn the present study, we decided to prepare and formulate a new chemotherapeutic drug (silver nanoparticles in ‎aqueous medium using Salvia officinalis leaf aqueous extract) for the treatment of human ovarian cancer in the in ‎vitro condition.Material and methodsThe organometallic chemistry tests such as Scanning Electron Microscopy (SEM), UV–Visible Spectroscopy ‎‎(UV-Vis), and Fourier Transformed Infrared Spectroscopy (FT‐IR) were used for characterizing of silver ‎nanoparticles. For investigating the antioxidant potentials of AgNO3, Salvia officinalis aqueous extract, and ‎silver nanoparticles, the DPPH test was used in the presence of butylated hydroxytoluene as the positive ‎control. To survey the cytotoxicity and anti-human ovarian cancer activities of AgNO3, Salvia officinalis ‎aqueous extract, and silver nanoparticles, MTT assay was used on the human ovarian cancer cell lines i.e., Caov-‎‎3‎, SK-OV-3, and PA-1‎. ‎ResultsIn UV-Vis, the clear peak in the wavelength of 421 nm indicated the formation of silver nanoparticles. In FT-IR ‎test, the presence of many antioxidant compounds with related bonds caused the excellent condition for ‎reducing of silver in the silver nanoparticles. The silver nanoparticles inhibited half of the DPPH molecules in ‎the concentration of 251 µg/mL. The best result of anti-human ovarian cancer effects of silver nanoparticles ‎against the above cell lines was observed in the case of the SK-OV-3 cell line. ‎ConclusionsSilver nanoparticles had very low cell viability and anti-human ovarian cancer properties dose-dependently ‎against Caov-3‎, SK-OV-3, and PA-1 cell lines without any cytotoxicity on the normal cell line (HUVECs). ‎

ABL1 Methylation Is a Distinct Molecular Event Associated With Clonal Evolution of Chronic Myeloid Leukemia

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2452-2460 ◽  
Author(s):  
Fotis A. Asimakopoulos ◽  
Pesach J. Shteper ◽  
Svetlana Krichevsky ◽  
Eitan Fibach ◽  
Aaron Polliack ◽  
...  
Keyword(s):  
Dna Repair ◽  
Stress Response ◽  
Chronic Myeloid Leukemia ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Clonal Evolution ◽  
Genotoxic Stress ◽  
Clinical Samples ◽  
Hematopoietic Progenitors

Methylation of the proximal promoter of the ABL1 oncogene is a common epigenetic alteration associated with clinical progression of chronic myeloid leukemia (CML). In this study we queried whether both the Ph′-associated and normal ABL1 alleles undergo methylation; what may be the proportion of hematopoietic progenitors bearing methylated ABL1 promoters in chronic versus acute phase disease; whether methylation affects the promoter uniformly or in patches with discrete clinical relevance; and, finally, whether methylation of ABL1 reflects a generalized process or is gene-specific. To address these issues, we adapted the techniques of methylation-specific PCR and bisulfite-sequencing to study the regulatory regions of ABL1 and other genes with a role in DNA repair or genotoxic stress response. In cell lines established from CML blast crisis, which only carry a single ABL1 allele nested within the BCR-ABL fusion gene, ABL1 promoters were universally methylated. By contrast, in clinical samples from patients at advanced stages of disease, both methylated and unmethylated promoter alleles were detectable. To distinguish between allele-specific methylation and a mixed cell population pattern, we studied the methylation status of ABL1 in colonies derived from single hematopoietic progenitors. Our results showed that both methylated and unmethylated promoter alleles coexisted in the same colony. Furthermore, ABL1 methylation was noted in the vast majority of colonies from blast crisis, but not chronic-phase CML. Both cell lines and clinical samples from acute-phase CML showed nearly uniform hypermethylation along the promoter region. Finally, we showed that ABL1 methylation does not reflect a generalized process and may be unique among DNA repair/genotoxic stress response genes. Our data suggest that specific methylation of the Ph′-associatedABL1 allele accompanies clonal evolution in CML.

Imatinib Is a Substrate for Various Multidrug Resistance Proteins

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4249-4249
Author(s):  
Krzysztof Czyzewski ◽  
Jan Styczynski
Keyword(s):  
Multidrug Resistance ◽  
Chronic Myeloid Leukemia ◽  
Cell Line ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Resistant Cell ◽  
Multidrug Resistance Proteins ◽  
Resistance Proteins ◽  
Imatinib Resistant ◽  
Ic50 Value

Abstract An increasing resistance to imatinib is an emerging problem in patients with chronic myeloid leukemia. The aim of the study was assessing possible mechanisms of cellular drug resistance in imatinib-resistant derivates of chronic myeloid leukemia K-562 cell line. A parental K-562 and its imatinib-resistant derivate cell lines were used. Cell lines were tested for cytotoxicity of imatinib, cytarabine, busulfan and etoposide. Multidrug resistance proteins expression, rhodamine retention and daunorubicin accumulation were measured for each cell line. Imatinib was cytotoxic to all tested groups of cells. Exposition of K-562 cell line to low concentrations of imatinib caused an increase of IC50 value of imatinib, while exposition of K-562 cell line to higher concentrations of imatinib decreased IC50 value of imatinib. There was a high correlation between PGP, MRP1 and LRP expression and IC50 for imatinib and etoposide. All tested cell lines were highly resistant to cytarabine. Rhodamine retention alone and in the presence of cyclosporine was the lowest in imatinib-resistant K-562R-0.1 cell line, what suggest high PGP activity in this cell line. Daunorubicin accumulation was the highest in parental K-562 cell line and it decreased in imatinib-resistant cell lines, which were characterized by high PGP, MRP1 and LRP expression. These data suggest that imatinib is a substrate for multidrug resistance proteins, and an increased expression of PGP, MRP1 and LRP play a role in resistance to imatinib in chronic myeloid leukemia.

B-lymphoid or myeloid lineage identity of cell lines derived from chronic myeloid leukemia blast crisis

2005 ◽  
Vol 161 (2) ◽  
pp. 187-188
Author(s):  
Bonaventure Ndikung Bejeng Soh ◽  
Florian Klein ◽  
Niklas Feldhahn ◽  
Markus Müschen
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Myeloid Lineage ◽  
Leukemia Blast ◽  
B Lymphoid

scholarly journals Absence of alternative splicing in bcr-abl mRNA in chronic myeloid leukemia cell lines

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 2066-2069 ◽  
Author(s):  
A Hermans ◽  
L Selleri ◽  
J Gow ◽  
GC Grosveld
Keyword(s):  
Alternative Splicing ◽  
Chronic Myeloid Leukemia ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Leukemia Cell ◽  
Specific Protein ◽  
S1 Nuclease ◽  
Ph Chromosome

Abstract The major consequence of the Philadelphia (Ph) translocation in chronic myeloid leukemia (CML) is the formation of a bcr-abl hybrid oncogene encoding a tumor cell-specific protein P210bcr-abl. In contrast to this, in Ph chromosome-positive acute lymphoblastic leukemia (Ph + ALL), a P190bcr-abl can be observed. This P190bcr-abl has been implicated in acute rather than chronic leukemogenesis. Therefore, it can be hypothesized that the transition from chronic to blast phase in CML is accompanied by an alternative splice in the bcr-abl mRNA, which results in a switch of the production of P210bcr-abl into P190bcr-abl. Initial S1 nuclease protection mapping supported this theory. However, this result appears to be based on an artifact in the S1 analysis. By using the polymerase chain reaction we provide evidence for the absence of alternative splicing in bcr-abl mRNA in two CML blast crisis cell lines.

Overexpression of SOCS-2 in advanced stages of chronic myeloid leukemia: possible inadequacy of a negative feedback mechanism

Blood ◽  
2002 ◽  
Vol 99 (5) ◽  
pp. 1766-1775 ◽  
Author(s):  
Beate Schultheis ◽  
Melina Carapeti-Marootian ◽  
Andreas Hochhaus ◽  
Andreas Weiβer ◽  
John M. Goldman ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Cell Lines ◽  
Negative Feedback ◽  
Myeloid Leukemia ◽  
Mononuclear Cells ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Feedback Mechanism ◽  
Cytokine Signaling ◽  
Negative Feedback Mechanism

Constitutive activation of the BCR-ABL tyrosine kinase is fundamental to the pathogenesis of chronic myeloid leukemia (CML). STI571 inhibits this activity and modulates the transcription of several genes. It was shown by differential display that the suppressor of cytokine signaling-2 (SOCS-2) gene was down-regulated by STI571 treatment in 14 of 16 BCR-ABL–positive cell lines and in 2 BCR-ABL–transfected murine lines, but not inBCR-ABL–negative counterparts. The effect was maximal at 2 hours and persisted for at least 24 hours after exposure to 1 μM STI571, whereas SOCS-1 and SOCS-3 expression were unaffected. Baseline levels of SOCS-2 were significantly higher in BCR-ABL–positive as compared withBCR-ABL–negative cell lines. It was similar in leukocytes and CD34+ cells from healthy persons (n = 44) and patients with CML in chronic phase (CP; n = 60) but significantly increased in patients with CML in blast crisis (BC; n = 20) (P < .0001). Mononuclear cells (MNCs) from 3 of 4 patients with CML in BC showed a 2-fold to 12-fold down-regulation ofSOCS-2 levels on in vitro exposure to STI571; moreover, a 2-fold to 11-fold decrease in SOCS-2 was observed in MNCs from 7 of 8 patients with CML in BC who responded to treatment with STI571. Refractoriness to STI571 or relapse after initial response was accompanied by augmentation of SOCS-2 expression. Ectopic overexpression of SOCS-2 in 32Dp210 cells slowed growth, inhibited clonogenicity, and increased their motility and sensitivity to STI571. Overall, the results suggest that SOCS-2 is a component of a negative feedback mechanism; it is induced by Bcr-Abl but cannot reverse its overall growth-promoting effects in blastic transformation.

scholarly journals Introducing a novel chemotherapeutic drug for the treatment of oral ‎squamous cell carcinoma‎: Silver nanoparticles green-formulated by ‎ ‎Matricaria chamomilla

2021 ◽  
Author(s):  
Rui Yang ◽  
Mingguo Wang ◽  
Xiaoxia Ma ◽  
Qing Gao
Keyword(s):  
Electron Microscopy ◽  
Squamous Cell Carcinoma ◽  
Silver Nanoparticles ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Butylated Hydroxytoluene ◽  
Matricaria Chamomilla ◽  
Chemotherapeutic Drug

IntroductionIn the present research, we formulated a modern chemotherapeutic drug by silver nanoparticles ‎‎(AgNPs) containing Matricaria chamomilla aqueous extract for the treatment of oral squamous ‎cell carcinoma.Material and methodsCharacterization of AgNPs was done by UV–Visible Spectroscopy (UV-Vis), Fourier ‎Transformed Infrared Spectroscopy (FT‐IR), Transmission Electron Microscopy (TEM), and ‎Field Emission Scanning Electron Microscopy (FE‐SEM). For investigating the antioxidant ‎properties of AgNO3, M. chamomilla, and AgNPs, the DPPH test was used in the presence of ‎butylated hydroxytoluene as the positive control. To survey the cytotoxicity and anti-oral ‎squamous cell carcinoma effects of AgNO3, M. chamomilla, and AgNPs, MTT assay was used ‎on the HSC-4, Ca9-22, and HSC-3 cell lines. ‎ResultsDPPH test revealed similar antioxidant potentials for M. chamomilla‎, AgNPs, and butylated ‎hydroxytoluene. Silver nanoparticles had very low cell viability and anti-oral squamous cell ‎carcinoma properties dose-dependently against HSC-4, Ca9-22, and HSC-3 cell lines without ‎any cytotoxicity on the normal cell line. The best result of anti-oral squamous cell carcinoma ‎properties of AgNPs against the above cell lines was seen in the case of the HSC-3 cell line. ‎ConclusionsAccording to the above findings, the silver nanoparticles containing M. chamomilla aqueous ‎extract can be administrated in humans for the treatment of several types of oral squamous cell ‎carcinoma. ‎

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