Induction of erythroid differentiation of human K562 cells by cisplatin analogs

Bianchi, Nicoletta; Ongaro, Federico; Chiarabelli, Cristiano; Gualandi, Licia; Mischiati, Carlo; Bergamini, Paola; Gambari, Roberto

doi:10.1016/s0006-2952(00)00297-5

Cited by 93 publications

(88 citation statements)

References 51 publications

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“…Cell Lines and Culture Conditions-Human erythroleukemia K562(S) cells (44) were cultured in a humidified atmosphere at 5% CO 2 in RPMI 1640 (Flow Laboratories) supplemented with 10% fetal bovine serum (CELBIO), 50 units/ml penicillin, and 50 g/ml streptomycin (45,46). Cell growth was studied by determining the cell number/ml after different days of in vitro cell culture (46).…”

Section: Synthetic Oligonucleotides and Peptidementioning

confidence: 99%

“…Cell growth was studied by determining the cell number/ml after different days of in vitro cell culture (46). Stock solutions of ara-C (100 M) were stored at Ϫ20°C in the dark and diluted immediately before use.…”

Section: Synthetic Oligonucleotides and Peptidementioning

confidence: 99%

“…The medium was not changed during the induction period. K562 cells containing heme or hemoglobin were detected by specific reaction with a benzidine/hydrogen peroxide solution as reported elsewhere (45,46). The final concentration of benzidine was 0.2% in 5 M glacial acetic acid, 10% H 2 O 2 (45,46).…”

Section: Synthetic Oligonucleotides and Peptidementioning

confidence: 99%

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Transcription Factor Decoy Molecules Based on a Peptide Nucleic Acid (PNA)-DNA Chimera Mimicking Sp1 Binding Sites

Borgatti¹,

Lampronti²,

Romanelli³

et al. 2003

Journal of Biological Chemistry

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Peptide nucleic acids (PNAs) are DNA-mimicking molecules in which the sugar-phosphate backbone is replaced by a pseudopeptide backbone composed of N-(2-aminoethyl)glycine units. We determined whether double-stranded molecules based on PNAs and PNA-DNA-PNA (PDP) chimeras could be capable of stable interactions with nuclear proteins belonging to the Sp1 transcription factor family and, therefore, could act as decoy reagents able to inhibit molecular interactions between Sp1 and DNA. Since the structure of PNA/PNA hybrids is very different from that of the DNA/DNA double helix, they could theoretically alter the molecular structure of the double-stranded PNA-DNA-PNA chimeras, perturbing interactions with specific transcription factors. We found that PNA-based hybrids do not inhibit Sp1/DNA interactions. In contrast, hybrid molecules based on PNA-DNA-PNA chimeras are very effective decoy molecules, encouraging further experiments focused on the possible use of these molecules for the development of potential agents for a decoy approach in gene therapy. In this respect, the finding that PDPbased decoy molecules are more resistant than DNA/ DNA hybrids to enzymatic degradation appears to be of great interest. Furthermore, their resistance can even be improved after complexation with cationic liposomes to which PDP/PDP chimeras are able to bind by virtue of their internal DNA structure.In vitro transfection of cis elements that decoy against nuclear factors leads to alteration of gene expression and was recently proposed in molecular medicine as a novel tool for the possible therapy of several disorders (1-12). One of the most effective decoy approaches so far described involves nuclear proteins belonging to the NF-B 1 superfamily (7-9, 13-20).Decoy molecules against NF-B inhibit the expression of NF-B regulated genes (MHC complex genes, IL2 receptor ␣, Igk, IL6, ␦ opioid receptor, preprogalanin, adhesion molecule-1) (20). More recently, dumbell DNA decoy elements against NF-B were demonstrated to be active in inhibiting ex vivo transcription driven by the long terminal repeat (LTR) of human immunodeficiency type-1 virus (HIV-1) (19). In addition to proteins belonging to the NF-B superfamily, decoy molecules for other target transcription factors, such as HNF-1, RFX1, nuclear factor YB, E2F, cAMP-response element, and Sp1, were found to be effective (1-6, 10 -12, 21).As to the molecular targets for the decoy approach, proteins belonging to the Sp1 family are of great interest since these transcription factors are involved in the regulation of the expression of several genes relevant to human pathologies, including those encoding vascular endothelial growth factor, plasminogen-activator inhibitor type-1 (PAI-1), COL1A2, urokinase-type plasminogen activator (uPA), and uPA receptor (3,(21)(22)(23)(24)(25). Sp1 binding sites are also present in the HIV-1 LTR (26). Thus, the development of experimental approaches based on Sp1 decoys to modulate the transcription of Sp1-dependent genes appears to be of great interest (3).Rec...

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Section: Synthetic Oligonucleotides and Peptidementioning

confidence: 99%

Section: Synthetic Oligonucleotides and Peptidementioning

confidence: 99%

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Transcription Factor Decoy Molecules Based on a Peptide Nucleic Acid (PNA)-DNA Chimera Mimicking Sp1 Binding Sites

Borgatti¹,

Lampronti²,

Romanelli³

et al. 2003

Journal of Biological Chemistry

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“…[8][9][10][11][12][13] In this respect, DNA-binding drugs appear to be of great interest. 14,15 These agents are known to modify the formation of DNA/nuclear protein complexes and thereby control gene expression. [16][17][18][19][20][21][22] Our research group has recently demonstrated that tallimustine 16 and some cisplatin analogs, 15 as well as the guanosinecytosine (GC)-rich binders chromomycin and mithramycin (MTH), 14 are powerful inducers of erythroid differentiation of the human leukemic K562 cell line, suggesting that the pattern of erythroid differentiation and of ␥-globin gene expression could be influenced by treatment with DNA-binding drugs.…”

Section: Introductionmentioning

confidence: 99%

Mithramycin induces fetal hemoglobin production in normal and thalassemic human erythroid precursor cells

Fibach

Bianchi

Borgatti

et al. 2003

Blood

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125

149

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We report in this paper that the DNAbinding drug mithramycin is a potent inducer of ␥-globin mRNA accumulation and fetal hemoglobin (HbF) production in erythroid cells from healthy human subjects and ␤-thalassemia patients. Erythroid precursors derived from peripheral blood were grown in 2-phase liquid culture. In this procedure, early erythroid progenitors proliferate and differentiate during phase 1 (in the absence of erythropoietin) into late progenitors. In phase 2, in the presence of erythropoietin, the latter cells continue their proliferation and mature into Hb-containing orthochromatic normoblasts. Compounds were added on days 4 to 5 of phase 2 (when cells started to synthesize Hb), and cells were harvested on day 12. Accumulation of mRNAs for ␥-globin, ␤-globin, ␣-globin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and ␤-actin were measured by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR); induction of HbF was analyzed by high-performance liquid chromatography (HPLC) and, at cellular level, by flow cytometry. We demonstrated that mithramycin was able to up-regulate preferentially ␥-globin mRNA production and to increase HbF accumulation, the percentage of HbF-containing cells, and their IntroductionPharmacologically mediated regulation of the expression of the human ␥-globin genes could be of interest as a potential therapeutic approach for hematologic disorders, including ␤-thalassemia and sickle cell anemia. [1][2][3][4][5][6][7][8] It is well established, indeed, that increase of fetal hemoglobin (HbF) to 30% of the total hemoglobin (Hb) leads to a significant improvement of the clinical status of patients affected by these hematologic disorders. 1-3 Therefore, current research has been focused on screening of various agents, such as hormones, cytotoxic drugs, hemopoietic cytokines, and short fatty acids as agents capable of augmenting HbF levels in humans. [8][9][10][11][12][13] In this respect, DNA-binding drugs appear to be of great interest. 14,15 These agents are known to modify the formation of DNA/nuclear protein complexes and thereby control gene expression. [16][17][18][19][20][21][22] Our research group has recently demonstrated that tallimustine 16 and some cisplatin analogs, 15 as well as the guanosinecytosine (GC)-rich binders chromomycin and mithramycin (MTH), 14 are powerful inducers of erythroid differentiation of the human leukemic K562 cell line, suggesting that the pattern of erythroid differentiation and of ␥-globin gene expression could be influenced by treatment with DNA-binding drugs. Interestingly, while chromomycin binding to DNA generates stable complexes, MTH-DNA complexes are highly unstable. 23 This could explain the low toxicity of MTH as compared with chromomycin. 24 For this reason, MTH was proposed as a therapeutic agent in several neoplastic diseases (such as chronic myelogenous leukemia and testicular cancer), 25 in Paget disease, 26 and in pathologies associated with hypercalcemia. 27,28 The main issue of the present paper w...

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“…3 Following erythroid induction, a sharp increase of expression of human ε and γ globin genes is observed in K562 cells, leading to a cytoplasmic accumulation of Hb Portland (ζ 2 γ 2 ) and Hb Gower 1 (ζ 2 ε 2 ), . [4][5][6][7] Among possible biological response modifiers, one of the most studied classes of compound is represented by short fatty acids, especially butyric and pivalic acids and related esters. Glycide  Authors for correspondence.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of glycose carbamides and evaluation of the induction of erythroid differentiation of human erythroleukemic K562 cells

Landi

Catelani

D’Andrea

et al. 2009

European Journal of Medicinal Chemistry

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A series of carbamides derived from 1,2:5,6-di-O-isopropylidene-D-gluco-(1) and D-allofuranose (3) as well as their 5,6-O-deprotected analogues (2 and 4) and methyl 3,4-O-isopropylidene-α-and β-D-galactopyranosides (5 and 6) have been prepared in order to evaluate their ability to induce erythroid differentiation of human erythroleukemic K562 cells. Twenty out of the 51 carbamides tested exhibit an appreciable activity as inducers of erythroid differentiation and have been fully characterised and described.

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Induction of erythroid differentiation of human K562 cells by cisplatin analogs

Cited by 93 publications

References 51 publications

Transcription Factor Decoy Molecules Based on a Peptide Nucleic Acid (PNA)-DNA Chimera Mimicking Sp1 Binding Sites

Transcription Factor Decoy Molecules Based on a Peptide Nucleic Acid (PNA)-DNA Chimera Mimicking Sp1 Binding Sites

Mithramycin induces fetal hemoglobin production in normal and thalassemic human erythroid precursor cells

Synthesis of glycose carbamides and evaluation of the induction of erythroid differentiation of human erythroleukemic K562 cells

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