Search results for "Neoplastic"
showing 10 items of 2901 documents
Colon Cancer Stem Cells: Promise of Targeted Therapy
2010
First developed for hematologic disorders, the concept of cancer stem cells (CSCs) was expanded to solid tumors, including colorectal cancer (CRC). The traditional model of colon carcinogenesis includes several steps that occur via mutational activation of oncogenes and inactivation of tumor suppressor genes. Intestinal epithelial cells exist for a shorter amount of time than that required to accumulate tumor-inducing genetic changes, so researchers have investigated the concept that CRC arises from the long-lived stem cells, rather than from the differentiated epithelial cells. Colon CSCs were originally identified through the expression of the CD133 glycoprotein using an antibody directed…
The Natural Fungal Metabolite Beauvericin Exerts Anticancer Activity In Vivo: A Pre-Clinical Pilot Study
2017
Recently, in vitro anti-cancer properties of beauvericin, a fungal metabolite were shown in various cancer cell lines. In this study, we assessed the specificity of this effect by comparing beauvericin cytotoxicity in malignant versus non-malignant cells. Moreover, we tested in vivo anticancer effects of beauvericin by treating BALB/c and CB-17/SCID mice bearing murine CT-26 or human KB-3-1-grafted tumors, respectively. Tumor size and weight were measured and histological sections were evaluated by Ki-67 and H/E staining as well as TdT-mediated-dUTP-nick-end (TUNEL) labeling. Beauvericin levels were determined in various tissues and body fluids by LC-MS/MS. In addition to a more pronounced …
Computational Evaluation and In Vitro Validation of New Epidermal Growth Factor Receptor Inhibitors
2020
Background:The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein that acts as a receptor of extracellular protein ligands of the epidermal growth factor (EGF/ErbB) family. It has been shown that EGFR is overexpressed by many tumours and correlates with poor prognosis. Therefore, EGFR can be considered as a very interesting therapeutic target for the treatment of a large variety of cancers such as lung, ovarian, endometrial, gastric, bladder and breast cancers, cervical adenocarcinoma, malignant melanoma and glioblastoma.Methods:We have followed a structure-based virtual screening (SBVS) procedure with a library composed of several commercial collections of chemicals (615,46…
Cytotoxicity of 4-hydroxy-N-(naphthalen-1-yl)-2-oxo-2H-chromene-3-carboxamide in multidrug-resistant cancer cells through activation of PERK/eIF2α/AT…
2021
After decades of research, multidrug resistance (MDR) remains a huge challenge in cancer treatment. In this study, the cytotoxic of 4-hydroxy-N-(naphthalen-1-yl)-2-oxo-2H-chromene-3-carboxamide (MCC1734) has been investigated towards multidrug-resistant cancer cell lines. MCC1734 exerted cytotoxicity on cell lines expressing different mechanisms of drug resistance (P-glycoprotein, BCRP, ABCB5, EGFR, p53 knockout) to a different extent. Interestingly, sensitive CCRF-CEM cells and multidrug-resistant P-gp-overexpressing CEM/ADR5000 cells represented similar sensitivity towards MCC1734, indicating MCC1734 can bypass P-gp-mediated resistance. Microarray-based mRNA expression revealed that MCC17…
Photoactivation of Anticancer Ru Complexes in Deep Tissue: How Deep Can We Go?
2017
Activation of anticancer therapeutics such as ruthenium (Ru) complexes is currently a topic of intense investigation. The success of phototherapy relies on photoactivation of therapeutics after the light passes through skin and tissue. In this paper, the photoactivation of anticancer Ru complexes with 671-nm red light through tissue of different thicknesses was studied. Four photoactivatable Ru complexes with different absorption wavelengths were synthesized. Two of them (Ru3 and Ru4) were responsive to wavelengths in the “therapeutic window” (650–900 nm) and could be activated using 671-nm red light after passing through tissue up to 16-mm-thick. The other two (Ru1 and Ru2) could not be ac…
Geldanamycin-induced osteosarcoma cell death is associated with hyperacetylation and loss of mitochondrial pool of heat shock protein 60 (hsp60)
2013
Osteosarcoma is one of the most malignant tumors of childhood and adolescence that is often resistant to standard chemo- and radio-therapy. Geldanamycin and geldanamycin analogs have been recently studied as potential anticancer agents for osteosarcoma treatment. Here, for the first time, we have presented novel anticancer mechanisms of geldanamycin biological activity. Moreover, we demonstrated an association between the effects of geldanamycin on the major heat shock proteins (HSPs) and the overall survival of highly metastatic human osteosarcoma 143B cells. We demonstrated that the treatment of 143B cells with geldanamycin caused a subsequent upregulation of cytoplasmic Hsp90 and Hsp70 w…
Synthesis and biological evaluation of a D-ring-contracted analogue of lamellarin D
2017
A D-ring contracted analogue of the strongly cytotoxic marine pyrrole alkaloid lamellarin D was synthesized and investigated for its antiproliferative action towards a wild type and a multidrug resistant (MDR) cancer cell line. The compound was found to inhibit tumor cell growth at submicromolar concentrations and showed a lower relative resistance in the MDR cell line than the antitumor drug camptothecin to which lamellarin D shows cross resistance and with which lamellarin D shares the same binding site.
Cyclic heptapeptides from the soil-derived fungus Clonostachys rosea
2019
Abstract Three new cyclic heptapeptides (1–3) together with three known compounds (4–6) were isolated from a solid rice culture of the soil-derived fungus Clonostachys rosea. Fermentation of the fungus on white beans instead of rice afforded a new γ-lactam (7) and a known γ-lactone (8) that were not detected in the former extracts. The structures of the new compounds were elucidated on the basis of 1D and 2D NMR spectra as well as by HRESIMS data. Compounds 1 and 4 exhibited significant cytotoxicity against the L5178Y mouse lymphoma cell line with IC50 values of 4.1 and 0.1 µM, respectively. Compound 4 also displayed cytotoxicity against the A2780 human ovarian cancer cell line with an IC50…
Mixed-ligand copper(ii)–sulfonamide complexes: effect of the sulfonamide derivative on DNA binding, DNA cleavage, genotoxicity and anticancer activity
2013
Four ternary complexes, [Cu(L1)2(bipy)] (1) [HL1 = N-(6-chlorobenzo[d]thiazol-2-yl)-4-methylbenzenesulfonamide], [Cu(L2)2(bipy)] (2) [HL2 = N-(benzo[d]thiazol-2-yl)-4-methylbenzenesulfonamide], [Cu(L3)2(bipy)]·1/2H2O (3) [HL3 = N-(5,6-dimethylbenzo[d]thiazol-2-yl)-4-methylbenzenesulfonamide] and [Cu(L4)2(bipy)] (4) [HL4 = N-(5,6-dimethylbenzo[d]thiazol-2-yl)benzenesulfonamide], were prepared and then characterized by X-ray crystallography, spectroscopy and magnetic measurements. Whereas the molecular structure of 1 and 2 consists of a discrete monomeric copper(II) species with a distorted square planar geometry, that of 3 and 4 consists of two independent molecules. In 3, both molecules pre…
Zinc overload mediated by zinc oxide nanoparticles as innovative anti-tumor agent
2017
The predicted global cancer burden is expected to surpass 20 million new cancer cases by 2025. Despite recent advancement in tumor therapy, a successful cancer treatment remains challenging. The emerging field of nanotechnology offers great opportunities for diagnosis, imaging, as well as treatment of cancer. Zinc oxide nanoparticles (ZnO NP) were shown to exert selective cytotoxicity against tumor cells via a yet unknown mechanism, most likely involving the generation of reactive oxygen species (ROS). These nanoparticles are a promising therapeutic opportunity as zinc is a nontoxic trace element and its application in medically-related products is considered to be safe. We could show that …