Search results for " Cell"
showing 10 items of 14074 documents
Synthesis and antiproliferative activity of a natural like glycoconjugate polycyclic compound
2016
Abstract A natural like O -glycoconjugate polycyclic compound 4 was obtained by a multistep procedure starting from N -(3-methyl-1-(4-nitrophenyl)-1 H -pyrazol-5-yl)acetamide. The glycosyl derivative 4 showed antiproliferative activity against all the tumoral cell lines of the NCI panel in the range 0.47–5.43 μ M. Cytofluorimetric analysis performed on MDA-MB231, a very aggressive breast cancer cell line, which does not express estrogen, progesterone and HER-2/neu receptors, showed that 4 is able to induce prolonged cell cycle arrest at G2/M phase and morphological signs of differentiation. These events are correlated with down-regulation of both cyclin B1 and cdc2, the cyclins involved in…
CHK1 inhibitor sensitizes resistant colorectal cancer stem cells to nortopsentin
2021
Summary Limited therapeutic options are available for advanced colorectal cancer (CRC). Herein, we report that exposure to a neo-synthetic bis(indolyl)thiazole alkaloid analog, nortopsentin 234 (NORA234), leads to an initial reduction of proliferative and clonogenic potential of CRC sphere cells (CR-CSphCs), followed by an adaptive response selecting the CR-CSphC-resistant compartment. Cells spared by the treatment with NORA234 express high levels of CD44v6, associated with a constitutive activation of Wnt pathway. In CR-CSphC-based organoids, NORA234 causes a genotoxic stress paralleled by G2-M cell cycle arrest and activation of CHK1, driving the DNA damage repair of CR-CSphCs, regardless…
Physiological concentrations of phytosterols enhance the apoptotic effects of 5-fluorouracil in colon cancer cells
2018
Abstract Combining natural products as co-adjuvants in 5-fluorouracil (5-FU) chemotherapy might enhance the effectiveness of 5-FU by avoiding a high dosage and/or reducing treatment times. We explored the anticancer efficacy of the phytosterols (PS) at concentrations achievable in the human colon, as well as their potential as sensitizing agents of human colon cancer cells (Caco-2 and HT-29) to 5-FU treatment. Cells proliferation, combination index, cell cycle, apoptosis, caspases activation, ROS production, and ΔΨm were determined. Co-treatment (PS+5-FU) had an antiproliferative additive effect, and moreover, in general a significantly improved efficacy was observed on cell cycle arrest at…
PTP1B phosphatase as a novel target of oleuropein activity in MCF-7 breast cancer model.
2019
Phosphatase PTP1B has become a therapeutic target for the treatment of type 2-diabetes, whereas recent studies have revealed that PTP1B plays a pivotal role in pathophysiology and development of breast cancer. Oleuropein is a natural, phenolic compound with anticancer activity. The aim of this study was to address the question whether PTP1B constitutes a target for oleuropein in breast cancer MCF-7 cells. The cellular MCF-7 breast cancer model was used in the study. The experiments were performed using cellular viability tests, Elisa assays, immunoprecipitation, flow cytometry analyses and computer modelling. Herein, we evidenced that the reduced activity of phosphatase PTP1B after treatmen…
[1,2]Oxazolo[5,4-e]isoindoles as promising tubulin polymerization inhibitors
2016
Abstract A series of [1,2]Oxazolo [5,4- e ]isoindoles has been synthesized through a versatile and high yielding sequence. All the new structures showed in the 1 HNMR spectra, the typical signal in the 8.34–8.47 ppm attributable to the H-3 of the [1,2]oxazole moiety. Among all derivatives, methoxy benzyl substituents at positions 3 and 4 or/and 5 were very effective in reducing the growth of different tumor cell lines, including diffuse malignant peritoneal mesothelioma (DMPM), an uncommon and rapidly malignancy poorly responsive to available therapeutic options. The most active compound 6j was found to impair tubulin polymerization, cause cell cycle arrest at G2/M phase and induce apoptosi…
Carob leaf polyphenols trigger intrinsic apoptotic pathway and induce cell cycle arrest in colon cancer cells
2017
IF 3.973; International audience; Chemoprevention of Colorectal cancer (CRC) is the major concern for improving public health. We investigated the protective effects of carob, Ceratonia siliqua L, leaf polyphenols (CLP) against CRC. Phenolic content analysis showed that CLP is enriched with gallic acid and m-coumaric acid. We observed that CLP exerted a dose dependent cytotoxic effect through the induction of apoptosis on CRC cell lines, with an IC50 around 20 mu g/mL CLP induced intrinsic apoptotic pathway through the caspase-9 activation and PARP cleavage in HCT-116 and CT-26 cells. Moreover, CLP induced cell cycle arrest in the G1 phase through p53 activation. Gallic acid and m-coumaric …
Design, synthesis, and biological evaluation of a new class of benzo[b]furan derivatives as antiproliferative agents, with in silico predicted antitu…
2018
A new series of 3-benzoylamino-5-(1H-imidazol-4-yl)methylaminobenzo[b]furans were synthesized and screened as antitumor agents. As a general trend, tested compounds showed concentration-dependent antiproliferative activity against HeLa and MCF-7 cancer cell lines, exhibiting GI50 values in the low micromolar range. In most cases, insertion of a methyl substituent on the imidazole moiety improved the antiproliferative activity. Therefore, methyl-imidazolyl-benzo[b]furans compounds were tested in cell cycle perturbation experiments, producing cell cycle arrest with proapoptotic effects. Their core similarity to known colchicine binding site binders led us to further study the structure featur…
Integrated molecular signaling involving mitochondrial dysfunction and alteration of cell metabolism induced by tyrosine kinase inhibitors in cancer.
2020
Cancer cells have unlimited replicative potential, insensitivity to growth-inhibitory signals, evasion of apoptosis, cellular stress, and sustained angiogenesis, invasiveness and metastatic potential. Cancer cells adequately adapt cell metabolism and integrate several intracellular and redox signaling to promote cell survival in an inflammatory and hypoxic microenvironment in order to maintain/expand tumor phenotype. The administration of tyrosine kinase inhibitor (TKI) constitutes the recommended therapeutic strategy in different malignancies at advanced stages. There are important interrelationships between cell stress, redox status, mitochondrial function, metabolism and cellular signali…
L-carnitine protects C2C12 cells against mitochondrial superoxide overproduction and cell death.
2017
International audience; AIMTo identify and characterize the protective effect that L-carnitine exerted against an oxidative stress in C2C12 cells.METHODSMyoblastic C2C12 cells were treated with menadione, a vitamin K analog that engenders oxidative stress, and the protective effect of L-carnitine (a nutrient involved in fatty acid metabolism and the control of the oxidative process), was assessed by monitoring various parameters related to the oxidative stress, autophagy and cell death.RESULTSAssociated with its physiological function, a muscle cell metabolism is highly dependent on oxygen and may produce reactive oxygen species (ROS), especially under pathological conditions. High levels o…
Role of TCTP for Cellular Differentiation and Cancer Therapy
2017
The translationally controlled tumor protein (TCTP) is a highly conserved protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side, tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic proteins of the Bcl-2 family and the p53 tumor suppressor protein. In this article, we draw attention to the …