Search results for "cell cycle"

Synthesis and Antitumor Activity of New Thiazole Nortopsentin Analogs

2016

New thiazole nortopsentin analogs in which one of the two indole units was replaced by a naphthyl and/or 7-azaindolyl portion, were conveniently synthesized. Among these, three derivatives showed good antiproliferative activity, in particular against MCF7 cell line, with GI50 values in the micromolar range. Their cytotoxic effect on MCF7 cells was further investigated in order to elucidate their mode of action. Results showed that the three compounds act as pro-apoptotic agents inducing a clear shift of viable cells towards early apoptosis, while not exerting necrotic effects. They also caused cell cycle perturbation with significant decrease in the percentage of cells in the G0/G1 and S ph…

The Putative Metal Coordination Motif in the Endonuclease Domain of Human Parvovirus B19 NS1 Is Critical for NS1 Induced S Phase Arrest and DNA Damage

2011

The non-structural proteins (NS) of the parvovirus family are highly conserved multi-functional molecules that have been extensively characterized and shown to be integral to viral replication. Along with NTP-dependent helicase activity, these proteins carry within their sequences domains that allow them to bind DNA and act as nucleases in order to resolve the concatameric intermediates developed during viral replication. The parvovirus B19 NS1 protein contains sequence domains highly similar to those previously implicated in the above-described functions of NS proteins from adeno-associated virus (AAV), minute virus of mice (MVM) and other non-human parvoviruses. Previous studies have show…

Apoptosis and cell cycle aberrations in epithelial odontogenic lesions : an evidence by the expression of p53, Bcl-2 and Bax

2017

Background Ameloblastoma (AMB), odontogenic keratocyst (OKC) and adenomatoid odontogenic tumor (AOT) are epithelial odontogenic lesions with diverse biologic profiles. Defects in regulation of apoptosis and cell cycle may be involved in the development and progression of those lesions, therefore we aimed to investigate the expression of Bcl-2, Bax and p53 to better understand the possible role of these proteins in AMBs, OKCs and AOTs. Material and Methods The studied sample consisted of 20 AMBs, 20 OKCs and 20 AOTs. Immunohistochemistry technique was performed for the antibodies p53, Bcl-2 and Bax. Immunoreactivity was observed in the epithelial component and positive cells were counted in …

ChemInform Abstract: Exploring the Anticancer Potential of Pyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-one Derivatives: The Effect on Apoptosis Induction…

2013

Abstract In order to investigate their anticancer potential, four new pyrazolo[1,2-a]benzo[1,2,3,4]tetrazinone derivatives, designed through the chemometric protocol VLAK, and three of the most active compounds of the previous series have been evaluated on some cellular events including proliferation, apoptosis induction, and cell cycle. The NCI one dose (10 μM) screening revealed that the 8,9-di-methyl derivative showed activity against Leukemia (CCRF-CEM) and Colon cancer cell line (COLO 205), reaching 81% and 45% of growth inhibition (GI), respectively. Replacement of the two methyl groups with two chlorine atoms maintained the activity toward Leukemia cell (CCRF-CEM, GI 77%) and selecti…

Purification by affinity chromatography of H1 RNA-Binding Proteins from rat brain

2003

Post-transcriptional regulation of mRNA metabolism is involved in processes as different as cell fate specification in development and cell response to a large variety of environmental cues. Regulation of all steps of RNA metabolism depends on RNA-binding proteins (RBPs). By using a T1 RNase protection assay, we previously identified three H1° RNA-binding factors (p40, p70 and p110), highly expressed in the rat brain. Here we report enrichment of these factors from brain extracts, obtained by affinity chromatography of biotinylated H1° RNA-protein complexes on streptavidin-conjugated paramagnetic particles. The purified proteins maintain RNA-binding ability and preference for histone messag…

Endoreduplication induced in cultured Chinese hamster cells by different anti-topoisomerase II chemicals

2005

With the ultimate purpose of testing the hypothesis that, as shown in yeast mutants, any malfunction of DNA topoisomerase II might result in aberrant mitosis due to defective chromosome segregation, we have chosen three chemicals of different nature, recently reported to catalytically inhibit the enzyme. The endpoint selected to assess any negative effect on the ability of topoisomerase II to properly carry out decatenation of fully replicated chromosomes in the G2/M phase of the cell cycle was the presence of metaphases showing diplochromosomes as a result of endoreduplication, i.e. two successive rounds of DNA replication without intervening mitosis. The anti-topoisomerase drugs selected …

Cytotoxicity of the Urokinase-Plasminogen Activator Inhibitor Carbamimidothioic Acid (4-Boronophenyl) Methyl Ester Hydrobromide (BC-11) on Triple-Neg…

2015

BC-11 is an easily synthesized simple thiouronium-substituted phenylboronic acid, which has been shown to be cytotoxic on triple negative MDA-MB231 breast cancer cells by inducing a perturbation of cell cycle when administered at a concentration equal to its ED50 at 72 h (117 μM). Exposure of cells to BC-11, either pre-absorbed with a soluble preparation of the N-terminal fragment of urokinase-plasminogen activator (uPa), or in co-treatment with two different EGFR inhibitors, indicated that: (i) BC-11 acts via binding to the N-terminus of the enzyme where uPa- and EGF receptor-recognizing sites are present, thereby abrogating the growth-sustaining effect resulting from receptor binding

Gene Expression Profile of Chronic Myeloid Leukemia Innately Resistant to Imatinib

2007

Background. Most chronic myeloid leukemia patients who receive imatinib as first line-terapy will obtain, after 12 months treatment, complete cytogenetic and molecular response . However several cases will not achieve molecular response, but their innate mechanism(s) of resistance remain poorly understood. We tried to explore the molecular events involved in innate resistance in CML. Study design. Five patients who were molecular “non responder” and seven “major” responder were investigated by using the expression profile of a set of 380 genes. Multiple testing procedure (MTP), Significance Analysis of Microarrays (SAM), Empirical Bayes Analysis of Microarrays (EBAM), False Discovery Rate (…

AQUEOUS EXTRACTS FROM LEAVES AND RHIZOMES OF THE MARINE SEAGRASS POSIDONIA OCEANICA EXHIBIT ANTI-LIVER CANCER ABILITY IN VITRO

2022

Effective targeting of breast cancer stem cells by combined inhibition of Sam68 and Rad51

2022

AbstractBreast cancer (BC) is the second cause of cancer-related deceases in the worldwide female population. Despite the successful treatment advances, 25% of BC develops resistance to current therapeutic regimens, thereby remaining a major hurdle for patient management. Current therapies, targeting the molecular events underpinning the adaptive resistance, still require effort to improve BC treatment. Using BC sphere cells (BCSphCs) as a model, here we showed that BC stem-like cells express high levels of Myc, which requires the presence of the multifunctional DNA/RNA binding protein Sam68 for the DNA-damage repair. Analysis of a cohort of BC patients displayed that Sam68 is an independen…