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Minerva Biotecnologica,
A M Saab,
I Lampronti,
A Finotti,
M Borgatti, R Gambari,
F Esseily,
S Safi,
M Diab-Assaf,
H Rabenau,
J Cinatl,
H W Doerr
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M.C. Dechecchi,
E. Nicolis,
P. Mazzi,
M. Paroni,
F. Cioffi,
A. Tamanini,
V. Bezzerri,
M. Tebon,
I. Lampronti,
S. Huang,
L. Wiszniewski,
M.T. Scupoli,
A. Bragonzi, R. Gambari,
G. Berton,
G. Cabrini
03/2012; , ISBN: 978-953-51-0287-8
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Minerva Biotecnologica,
A M Saab,
I Lampronti,
A Finotti,
M Borgatti, R Gambari,
F Esseily,
S Safi,
M Diab-Assaf,
H Rabenau,
J Cinatl,
H W Doerr
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ABSTRACT: In vitro evaluation of the biological activity of Lebanese medicinal plants extracts against herpes simplex virus type 1 Medicinal plants extracts are interesting novel drugs for use as antimicrobial and antiviral agents. In this study we investigate the in vitro antiviral activity of eight ethanol medicinal plant extracts against Herpes simplex virus (HSV-1) infection on monkey kidney cel-ls. Acyclovir, an antiviral agent currently applied for treatment of herpes virus type 1 infection, was used to compare the plant extracts therapeutic activity. The inhibitory concentrations (IC 50) were determi-ned for eight medicinal plants extracts obtained from the following plants: Calamintha origanifolia, Satu-reja thymbra, Prangos aspurela, Sidiritis Perfoliata, Aspurela glomerata, Erythreae Centaurium, Hysso-pus officinalis and Salvia accetabulosa. Cytotoxicity was evaluated by MTT assay in Vero cells. The selec-tive index (SI) of these medicinal plant extracts was used to prove the therapeutic activity. We found that C. origanifolia and S.thymbra extracts have the highest selective index (SI) in our data and are therefore po-tentially be used for treatment of HSV-1 disease.
Minerva Biotecnologica 01/2012; 24. · 0.26 Impact Factor
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E Torreggiani,
C Bianchini,
L Penolazzi,
E Lambertini,
R Vecchiatini,
A Canella, R Gambari,
E Magri,
S Pelucchi,
A Pastore,
R Piva
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ABSTRACT: The research addressed to detect new molecular targets in the development of therapeutic strategies aimed to repair bone tissues. The AIM OF THIS STUDY was to determine the potential osteogenic activity of bone cells from the nasal septum and their use to perform accurate molecular analysis from a single sample.
The cells, after nasal septum surgery, were subjected to gene silencing, Reverse Transcriptase - Polymerase Chain reactions, immunocytochemistry and chromatin immunoprecipitation.
Cells from the nasal septum can give rise to mature osteoblasts that express osteogenic markers (ALP, Runx2, Slug) and are able to mineralize. We demonstrated that Runx2, a transcription factor critical in early osteospecific differentiation, interacts in vivo with the promoter of the SLUG gene, a marker of osteoblast maturation.
We demonstrated that nasal septum-derived osteoblasts represent an interesting alternative source for bone forming cells, and a promising material to be utilized in bone cellular therapy.
Rhinology 06/2011; 49(2):148-54. · 1.32 Impact Factor
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G Cabrini,
V Bezzerri,
I Mancini,
E Nicolis,
M C Dechecchi,
A Tamanini,
I Lampronti,
L Piccagli,
N Bianchi,
M Borgatti, R Gambari
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ABSTRACT: The development of drugs able to inhibit the expression of pro-inflammatory genes is of great interest in the treatment of cystic fibrosis (CF). Chronic pulmonary inflammation in the lungs of patients affected by CF is characterized by massive intra-bronchial infiltrates of neutrophils. This process is initiated upon interaction of pathogens (including Pseudomonas aeruginosa) with surface bronchial cells. Consequently, they release cytokines, the most represented being the potent neutrophilic chemokine Interleukin (IL)-8 and the pro-inflammatory cytokine IL-6. The chronic inflammatory process is crucial, since it leads to progressive tissue damage and severe respiratory insufficiency. In order to reduce the adverse effects of the excessive inflammatory response, one of the approaches leading to inhibition of IL-8 and IL-6 gene expression is the transcription factor (TF) decoy approach, based on intracellular delivery of double stranded oligodeoxynucleotides (ODNs) mimicking the binding sites of TFs and causing inhibition of binding of TF-related proteins to regulatory sequences identified in the promoters of specific genes. Since the promoters of IL-8 and IL-6 contain consensus sequences for NF-κ B and Sp1, double stranded TF "decoy" ODNs targeting NF-κB and Sp1 can be used. Alternatively, screening of drugs targeting relevant TFs can be performed using drug cocktails constituted by extracts from medicinal plants inhibiting TF/DNA interactions. Finally, virtual screening might lead to identification of putative bioactive molecules to be validated using molecular and cellular approaches. By these means, low-molecular drugs targeting NF-κB and inhibiting IL-8 gene expression are available for pre-clinical testing using experimental systems recapitulating chronic pulmonary inflammation of patients affected by CF.
Current Medicinal Chemistry 10/2010; 17(35):4392-404. · 4.86 Impact Factor
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ABSTRACT: Precisely manipulating and sorting live cells on a lab on a chip is still a major challenge. This article shows how to use dielectrophoresis for cell sorting. The authors also describe a prototype CMOS chip with a sensor-actuator array, row-column addressing logic and readout circuitry. In this article, we examine the new microelectronic technology that gives scientists the ability to monitor, sort, and analyze vast populations of cells and interact with each cell individually. A microelectronic platform called a lab on a chip (LoC) allows precise manipulation of cells with no effect on their phenotypes. The motivation for developing this technology is that investigations in recent years have shown that a few cells changing their behavior unexpectedly can induce deadly diseases such as cancer. Current LoC design and manufacturing techniques are spawning new biotechnology methods with potential for research, diagnosis, and therapy.
IEEE Design and Test of Computers 02/2007; · 1.39 Impact Factor
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ABSTRACT: The essential oils obtained from different officinal
plants of Lebanon, belonging to the Magnoliophyta division,
have been tested for their antiproliferative activity on human
erythroleukemic K562 cells. Satureja montana showed the
most interesting biological activity in inhibiting the cell growth
and inducing erythroid differentiation of K562 cells. The
essential oil of Satureja montana was therefore analyzed using
a GC/MS (gas chromatography/mass spectrometry) system in
order to identify the major constituents and compare them with
analysis performed on Satureja hortensis. We demonstrated
that the essential oil composition varied with the species, the
major constituent of Satureja hortensis being carvacrol
(50.61%) and that of Satureja montana being ·-terpineol
(12.66%). In order to identify molecules possibly responsible
for the biological activity, commercially available derivatives
have been assayed on the K562 cell line. Satureja montana
essential oil displayed different natural derivatives characterized
by higher activity than those present in Satureja hortensis.
The common active principles are ·-pinene, Á-terpinene,
4-terpineol, ·-terpineol, Ù-cadinene, Ù-cadinol and caryophyllene.
Both caryophyllene and ·-terpineol showed important
antiproliferative effects on K562 cells.
Introduction
Int.J. of oncology.volume 29,number 4,October 2006.P.989-995. 01/2006;
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ABSTRACT: In this paper we investigated how the increase of human estrogen receptor alfa (ERalpha) gene expression may affect breast, osteoblast and osteoclast cells. Increase of ERalpha expression was obtained by interfering with the activity of a negative transcription factor and by removing it with a short and powerful decoy oligonucleotide (RA4-3') mimicking a region of distal promoter C of ERalpha gene. We provide evidence that this decoy was able to induce apoptosis in osteoclasts, but not in osteoblasts and in breast cancer cells, in an estrogen dependent manner. This effect was associated with increase of the levels of Caspase 3 and Fas receptor. Since ERalpha is important in the transcription of different genes and is involved in several pathological processes, including neoplastic and osteopenic diseases, our findings may be of relevance for a possible new therapeutical approach of such diseases.
APOPTOSIS 11/2005; 10(5):1079-94. · 4.79 Impact Factor
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ABSTRACT: Several medicinal plants can be employed to produce extracts exhibiting biological effects. The aim of this work was to verify the ability of extracts derived from different medicinal plants of Bangladesh in interfering with specific DNA-protein interactions. The rationale for this study is based on the observation that alteration of gene transcription represents a very promising approach to control the expression of selected genes and could be obtained using different molecules acting on the interactions between DNA and transcription factors (TFs). We have analysed the antiproliferative activity of extracts from the medicinal plants Hemidesmus indicus, Polyalthia longifolia, Aphanamixis polystachya, Moringa oleifera, Lagerstroemia speciosa, Paederia foetida, Cassia sophera, Hygrophila auriculata and Ocimum sanctum. Antiproliferative activity was assayed on different human cell lines, including erythroleukemia K562, B-lymphoid Raji, T-lymphoid Jurkat and erythroleukemia HEL cell lines. We employed the electrophoretic mobility shift assay (EMSA) as a suitable technique for the identification of plant extracts altering the binding between transcription factors and the specific DNA elements. We found that low concentrations of Hemidesmus indicus, Polyalthia longifolia, Moringa oleifera and Lagerstroemia speciosa, and very low concentrations of Aphanamixis polystachya extracts inhibit the interactions between nuclear factors and target DNA elements mimicking sequences recognized by the nuclear factor kappaB (NF-kappaB). On the contrary, high amount of extracts from Paederia foetida, Cassia sophera, Hygrophila auriculata or Ocimum sanctum were unable to inhibit NF-kappaB/DNA interactions. Extracts inhibiting both NF-kappaB binding activity and tumor cell growth might be a source for anti-tumor compounds, while extracts inhibiting NF-kappaB/DNA interactions with lower effects on cell growth, could be of interest in the search of compounds active in inflammatory diseases, for which inhibition of NF-kappaB binding activity without toxic effects should be obtained.
Medicinal Chemistry 08/2005; 1(4):327-33. · 1.50 Impact Factor
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M Borgatti,
A Finotti,
A Romanelli,
M Saviano,
N Bianchi,
I Lampronti,
E Lambertini,
L Penolazzi,
C Nastruzzi,
C Mischiati,
R Piva,
C Pedone, R Gambari
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ABSTRACT: Peptide nucleic acids (PNAs)-DNA chimeras have been recently described as DNA mimics constituted of a part of PNA and of a part of DNA. We have demonstrated that double stranded molecules based on PNA-DNA chimeras bind to transcription factors in a sequence-dependent manner. Accordingly, these molecules can be used for transcription factor decoy (TFD) pharmacotherapy. Effects of double stranded PNA-DNA chimeras targeting NF-kappaB and Sp1 were determined on in vitro cultured human cells and were found to be comparable to those observed using double-stranded DNA decoys. The TFD molecules based on PNA-DNA chimeras can be further engineered by addition of short peptides facilitating cell penetration and nuclear localization. Therefore, these engineered molecules could be of great interest for in vivo experiments for non-viral gene therapy of a variety of diseases, including neoplastic and viral diseases, for which the TFD approach has been already demonstrated as a very useful strategy.
Current Drug Targets 12/2004; 5(8):735-44. · 3.55 Impact Factor
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ABSTRACT: In this study we describe an original, efficient, and innovative printed circuit board (PCB) device able to generate dielectrophoresis-based, software-controlled cages that can be moved to any place inside a microchamber. Depending on their dielectrophoretic properties, eukaryotic cells can be "entrapped" in cages and moved under software control. The main conclusion gathered from the experimental data reported is that the PCB device based on dielectrophoresis permits levitation and movement of different tumor cells at different dielectrophoresis conditions. The results presented herein are therefore the basis for experiments aimed at forced interactions or separation of eukaryotic cells using "lab-on-a-chip." In fact, because many cages can be controlled at the same time, and two or more cages can be forced to share the same or a different location, it is possible, in principle, either to bring in contact cells of a differing histotype or to separate them.
Biotechnology and Bioengineering 06/2003; 82(4):474-9. · 3.95 Impact Factor
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ABSTRACT: In the present paper we show that extracts from Aegle marmelos Correa are able to inhibit the in vitro proliferation of human tumor cell lines, including the leukemic K562, T-lymphoid Jurkat, B-lymphoid Raji, erythroleukemic HEL, melanoma Colo38, and breast cancer MCF7 and MDA-MB-231 cell lines. Molecules present within the studied Aegle marmelos C. extracts were identified by gas-chromatography/mass-spectrometry analysis; three derivatives (butyl p-tolyl sulfide, 6-methyl-4-chromanone and butylated hydroxyanisole) were found to exhibit strong activity in inhibiting in vitro cell growth of human K562 cells. The antiproliferative activity of these compounds was found to be comparable to that of known antitumor agents, including cisplatin, chromomycin, cytosine arabinoside and 5-fluorouracil. In addition, the antiproliferative activity of butyl-p-tolyl sulfide, 6-methyl-4-chromanone and 5-methoxypsolaren was associated to activation of the differentiation pattern of K562 cells.
Phytomedicine 06/2003; 10(4):300-8. · 3.27 Impact Factor
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ABSTRACT: Sangre de Drago is a red viscous latex extracted from Croton lechleri (Euphorbiaceae) cortex, renowned in South American popular medicine for its wound-healing properties. The in vitro antiproliferative effects were determined on the human myelogenous leukemia K562 cells line (IC50 = 2.5 +/- 0.3 microg ml(-1)). The mutagenic and antimutagenic activity of C. lechleri sap was examined by means of the Ames/Salmonella test. No mutagenic activity was found on the Salmonella typhimurium strains T98 and T100, either with or without S9 activation. On the other hand, the sap showed an inhibitory effect against the mutagenic activity of the indirectly acting mutagen 2-Aminoanthracene in presence of S9 and a moderate protective activity against directly acting mutagens Sodium Azide and 2-Nitrofluorene. Therefore we suggest that C. lechleri sap interacts with the enzymes of the S9 mix, thereby inhibiting the transformation of 2-Aminoantracene into its active forms.
Phytomedicine 04/2003; 10(2-3):139-44. · 3.27 Impact Factor
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ABSTRACT: Due to the scarcity of available human livers, porcine hepatocytes are currently being evaluated as a xenogeneic cell source for extracorporeal bioartificial liver (BAL). Hypothermic storage of isolated porcine hepatocytes could support stocking of cell-loaded bioreactors for BAL use and may provide bioreactors ready to be used at the patient's bedside. For the development of this technology, it is of utmost importance to ensure cell viability and differentiated functions after low-temperature storage and following warm reperfusion. We compared cell viability, functional activity and apoptosis in isolated porcine hepatocytes which were perfused within a radial-flow bioreactor (RFB), stored at 4 degrees C and then reperfused at 37 degrees C. RFBs were loaded with 8 x 10(9), > or = 90% viable hepatocytes at 37 degrees C for 3 h. RFBs were then flushed with 4 degrees C University of Wisconsin solution (UW) and subsequently stored for 24 h or 48 h. RFBs were then reperfused for 8 h with recirculating medium plus serum at 37 degrees C . Cytochrome P450 (CYP) activity was studied before and after cold storage by means of monoethylglycinexylide (MEGX) detection in the effluent medium, after repeated lidocaine injections. After reperfusion experiments, hepatocytes were harvested for total RNA isolation. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used in order to amplify specific mRNAs for Bcl-2 and Bax genes, by using appropriate primers; beta-actin primers were used as control. Total RNA was extracted by northern blotting analysis and for Bcl-2, Bax and beta-actin RNA messenger detection, RT-PCR amplification was used. Freshly isolated hepatocytes perfused into the RFB showed a progressive increase of MEGX while a loss in Bax expression was paralleled by an increase in Bcl-2 expression, in comparison to starting hepatocytes. After 4 degrees C storage and warm reperfusion, MEGX production was preserved in 24 h- and 48 h-stored bioreactors as well as a sharp increase of Bcl-2 and a decrease of Bax mRNAs. Our study suggests that refrigeration of hepatocyte-bioreactors is a suitable strategy to maintain both viability and function of isolated hepatocytes, for up to 48 h a time-length that is compatible with long-distance delivery of ready-to-use bioreactors.
The International journal of artificial organs 02/2003; 26(2):139-48. · 1.86 Impact Factor
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ABSTRACT: The decoy approach against nuclear factor kappaB (NF-kappaB) is a useful tool to alter NF-kappaB dependent gene expression using synthetic oligonucleotides (ODNs) carrying NF-kappaB specific cis-elements. Unfortunately, ODNs are not stable and need to be be extensively modified to be used in vivo or ex vivo. We have previously evaluated the possible use of peptide nucleic acids (PNAs) as decoy molecules. The backbone of PNAs is composed of N-(2-aminoethyl)glycine units, rendering these molecules resistant to both nucleases and proteases. We found that the binding of NF-kappaB transcription factors to PNAs was either very low (binding to PNA-PNA hybrids) or exhibited low stability (binding to PNA-DNA hybrids). The main consideration of the present paper was to determine whether PNA-DNA chimeras mimicking NF-kappaB binding sites are capable of stable interactions with proteins belonging to the NF-kappaB family. Molecular modeling was employed for the design of PNA-DNA chimeras; prediction of molecular interactions between chimeras and NF-kappaB nuclear proteins were investigated by molecular dynamics simulations, and interactions between PNA-DNA chimeras and NF-kappaB proteins were studied by gel shifts. We found significant differences between the structure of duplex NF-kappaB PNA-DNA chimera and duplex NF-kappaB DNA-DNA. However, it was found that these differences do not prevent the duplex PNA-DNA chimera from binding to NF-kappaB transcription factors, being able to suppress the molecular interactions between HIV-1 LTR and p50, p52 and nuclear factors from B-lymphoid cells. Therefore, these results demonstrate that the designed NF-kappaB DNA-PNA chimeras could be used for a decoy approach in gene therapy.
European Journal of Biochemistry 01/2002; 268(23):6066-75. · 3.58 Impact Factor
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R Gambari
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ABSTRACT: Peptide nucleic acids (PNAs) represent nucleic acid analogues with unique biochemical properties and of great interest for the development of therapeutic agents. The firstly designed and tested PNAs are molecules in which the sugar-phosphate backbone of DNA was replaced with a pseudopeptide chain constituted by N-(2-aminoethyl) glycine monomers. Nucleobases can be linked to this backbone through a carboxymethyl moiety, which allows to maintain a two atom spacer between the backbone and the bases. Since the first reports on PNAs based on N-(2-aminoethyl) glycine backbone, other PNA analogues have been synthesized, with the main purpose of improve biological activities as well as stability and efficient delivery to target cells. Of great interest are chiral PNAs, PNA analogues bearing phosphate groups (PHONA), PNA-DNA and PNA-peptide chimeras, PNA linked to non-peptide vectors. PNAs hybridize to DNA and RNA with high efficiency following the Watson-Crick hybridization rules, forming highly stable PNA/DNA and PNA/RNA duplexes. In addition, homopyrimidine PNAs, as well as PNAs containing a high pyrimidine:purine ratio, are able to bind to DNA or RNA forming highly stable (PNA)(2)-DNA triple helices. Accordingly, therapeutic PNA and PNA analogues could act as antigéne as well as antisense molecules. In addition, recent studies provide evidences for the possible use of PNA-based therapeutic molecules as artificial promoters, as decoy or ribozyme facilitator. Among the therapeutic applications of PNA-based molecules, the most pomising include anti-cancer and anti-viral experimental strategies, but activity of PNAs against bacteria and medically important parasitic organisms have been also reported.
Current Pharmaceutical Design 12/2001; 7(17):1839-62. · 3.87 Impact Factor
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R Gambari
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ABSTRACT: The applications of surface plasmon resonance (SPR) and biosensor technology for biospecific interaction analysis (BIA) of molecular interactions between transcription modifiers and target biomolecules is here described for the identification of possible candidates for drug research and development in antitumor and antiviral therapy. SPR-based BIA offers many advantages with respect to most of the other available methodologies to study biomolecular interactions. It should be underlined that (a) most commercially available biosensors are fully automated instruments; (b) no labelling is required; (c) a large variety of activated sensor chips are commercially available allowing the immobilization of either proteins or target DNA or RNA; (d) the amount of both ligand and analyte needed to obtain informative results is low; (e) the assay is rapid and (f) the sensor chip could be re-used many times, leading to low running costs, with the only limitation of verifying the stability of the immobilized ligand. Approaches employing SPR-based BIA were described for the development of (a) triple-helix forming oligonucleotides (TFO) and peptide nucleic acids (PNAs), (b) DNA-binding drugs, (c) decoy molecules and (d) PNAs able to perform strand invasion. All these biomolecules are of great interest for the development of transcription modifiers. Since alteration of the expression of transcription factors is involved in tumor cell growth and metastasis, SPR-based BIA appears to be a methodology of great impact in the design and development of anti-cancer agents.
Current Medicinal Chemistry - Anti-Cancer Agents 12/2001; 1(3):277-91.
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ABSTRACT: In this paper we demonstrate that peptide nucleic acids (PNAs) are excellent probes able to detect the W1282X point mutation of the cystic fibrosis (CF) gene when biospecific interaction analysis (BIA) by surface plasmon resonance (SPR) and biosensor technologies is performed. The results reported here suggest that BIA is an easy, fast, and automatable approach for detecting mutations of CF, allowing real-time monitoring of hybridization between 9-mer CF PNA probes and target biotinylated PCR products generated from healthy, heterozygous subjects and homozygous W1282X samples and immobilized on streptavidin-coated sensor chips. This method is, to our knowledge, the first application of PNAs, BIA, and SPR to a human hereditary mutation, and demonstrates the feasibility of these approaches for discriminating between normal and mutated target DNA. We like to point out that the procedure described in this paper is rapid and informative; results are obtained within a few minutes. This could be of great interest for molecular pre-implantation diagnosis to discriminate homozygous CF embryos from heterozygous and healthy embryos. Other advantages of the methodology described in the present paper are (a) that it is a nonradioactive methodology and (b) that gel electrophoresis and/or dot-spot analysis are not required. More importantly, the demonstration that SPR-based BIA could be associated with microarray technology allows us to hypothesize that the method described in the present paper could be used for the development of a protocol employing multispotting on SPR biosensors of many CF-PCR products and a real-time simultaneous analysis of hybridization to PNA probes. These results are in line with the concept that SPR could be an integral part of a fully automated diagnostic system based on the use of laboratory workstations, biosensors, and arrayed biosensors for DNA isolation, preparation of PCR reactions, and identification of point mutations.
Laboratory Investigation 11/2001; 81(10):1415-27. · 3.64 Impact Factor
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ABSTRACT: We have investigated the effects of aromatic polyamidines on HIV-1 transcription. We found a block to Tat-induced HIV-1 transcription assessed by inhibition of CAT activity in HL3T1 cells at a concentration lower than the IC50 value, suggesting that molecules with three (TAPB) and four (TAPP) benzamidine rings could be useful against HIV-1. In contrast, aromatic polyamidines with only two benzamidine rings (DAPP) did not block Tat-induced transcription. We reasoned that this effect could be due to binding of TAPB and TAPP to HIV-1 TAR RNA. By EMSA and filter binding assays, we studied possible interactions of aromatic polyamidines with HIV-1 TAR RNA. Wild-type TAR RNA or TAR RNA with mutations in the stem or bulge sequences, but retaining the stem-loop structure, was used to define the RNA-binding activities of these compounds. Our data suggest that aromatic polyamidines with two (DAPP) and four (TAPP) benzamidine rings, respectively, do not bind to TAR RNA or bind without sequence selectivity. Interestingly, an aromatic polyamidine with three benzamidine rings (TAPB) recognizes the wild-type TAR RNA in a specific manner. Furthermore, we found that introduction of one halogen atom into the benzamidine rings strongly increases the RNA-binding activity of these compounds.
Antisense and Nucleic Acid Drug Development 09/2001; 11(4):209-17.
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ABSTRACT: Human leukaemic K562 cells can be induced in vitro to erythroid differentiation by a variety of chemical compounds, including haemin, butyric acid, 5-azacytidine, cytosine arabinoside, mithramycin and chromomycin, cisplatin and cisplatin analogues. Differentiation of K562 cells is associated with an increase of expression of embryo-fetal globin genes, such as the zeta-, epsilon- and gamma-globin genes. The K562 cell line has been proposed as a very useful in vitro model system to determine the therapeutic potential of new differentiating compounds as well as to study the molecular mechanism(s) regulating changes in the expression of embryonic and fetal human globin genes. Inducers of erythroid differentiation stimulating gamma-globin synthesis could be considered for possible use in the therapy of haematological diseases associated with a failure in the expression of normal beta-globin genes. We have analysed the effects of tallimustine and distamycin on cell growth and differentiation of K562 cells. The results demonstrated that tallimustine is a potent inducer, while distamycin is a weak inducer, of K562 cell erythroid differentiation. Erythroid differentiation was associated with an increase of accumulation of gamma-globin mRNA and of production of both haemoglobin (Hb) Gower 1 and Hb Portland. In addition, tallimustine-mediated erythroid induction occurred in the presence of activation of the apoptotic pathway. The reasons for proposing tallimustine as an inducer of gamma-globin gene expression are strongly sustained by the finding that this compound stimulates fetal haemoglobin production in human erythroid precursor cells from normal subjects.
British Journal of Haematology 07/2001; 113(4):951-61. · 4.94 Impact Factor
