Search results for "death"
showing 10 items of 1744 documents
Synthesis and photocytotoxic activity of [1,2,3]triazolo[4,5-h][1,6]naphthyridines and [1,3]oxazolo[5,4-h][1,6]naphthyridines
2018
Abstract [1,2,3]Triazolo[4,5-h][1,6]naphthyridines and [1,3]oxazolo[5,4-h][1,6]naphthyridines were synthesized with the aim to investigate their photocytotoxic activity. Upon irradiation, oxazolo-naphtapyridines induced light-dependent cell death at nanomolar/low micromolar concentrations (EC50 0.01–6.59 μM). The most photocytotoxic derivative showed very high selectivity and photocytotoxicity indexes (SI = 72–86, PTI>5000), along with a triplet excited state with exceptionally long lifetime (18.0 μs) and high molar absorptivity (29781 ± 180 M−1cm−1 at λmax 315 nm). The light-induced production of ROS promptly induced an unquenchable apoptotic process selectively in tumor cells, with mitoch…
N-acetylglycoside of oleanolic acid (aridanin) displays promising cytotoxicity towards human and animal cancer cells, inducing apoptotic, ferroptotic…
2020
Abstract Background The discovery of novel phytochemicals represents a reasonable approach to fight malignancies, especially those which are resistant to standard chemotherapy. Purpose We evaluated the cytotoxic potential of a naturally occurring N-acetylglycoside of oleanolic acid, aridanin, on 18 cancer cell lines, including sensitive and drug-resistant phenotypes mediated by P-glycoprotein, BCRP, p53 knockout, deletion-mutated EGFR, or BRAF mutations. Furthermore, metastasizing B16/F10 cells, HepG2 hepatocarcinoma and normal AML12 hepatocytes were investigated. The mechanisms of aridanin-induced cell death was further investigated. Methods The resazurin reduction assay (RRA) was applied …
Death receptors as targets in cancer
2013
Anti-tumour therapies based on the use PARAs (pro-apoptotic receptor agonists), including TRAIL (TNF-Related Apoptosis inducing Ligand) or monoclonal antibodies targeting TRAIL-R1 or TRAIL-R2, have been disappointing so far, despite clear evidence of clinical activity and lack of adverse events for the vast majority of these compounds, whether combined or not with conventional or targeted anti-cancer therapies. This brief review aims at discussing the possible reasons for the lack of apparent success of these therapeutic approaches and at providing hints in order to rationally design optimal protocols based on our current understanding of TRAIL signalling regulation or resistance for future…
Cucurbitacins as inducers of cell death and a rich source of potential anticancer compounds.
2011
Triterpenes have been reported to induce cell death. One relevant group of this family of compounds is cucurbitacins, which have been studied as inducers of apoptosis in various cancer cell lines. The most significant mechanisms with regard to the apoptotic effects of cucurbitacins are their ability to modify transcriptional activities via nuclear factors or genes and their capability to activate or inhibit pro- or anti-apoptotic proteins. Still, while the majority of studies on these compounds have dealt with their apoptotic effects on cancer cell lines, several research groups have also explored their anti-inflammatory activities. In general, cucurbitacins are considered to be selective i…
Enhanced oxidative stress and increased mitochondrial mass during Efavirenz-induced apoptosis in human hepatic cells
2010
BACKGROUND AND PURPOSE Efavirenz (EFV) is widely used in the treatment of HIV-1 infection. Though highly efficient, there is growing concern about EFV-related side effects, the molecular basis of which remains elusive. EXPERIMENTAL APPROACH In vitro studies were performed to address the effect of clinically relevant concentrations of EFV (10, 25 and 50 µM) on human hepatic cells. KEY RESULTS Cellular proliferation and viability were reduced in a concentration-dependent manner. Analyses of the cell cycle and several cell death parameters (chromatin condensation, phosphatidylserine exteriorization, mitochondrial proapoptotic protein translocation and caspase activation) revealed that EFV trig…
Flupirtine increases the levels of glutathione and Bcl-2 in hNT (human ) neurons: mode of action of the drug-mediated anti-apoptotic effect
1996
Flupirtine is a triaminopyridine analogue which has been successfully applied in clinics as a non-opiate analgesic drug. Previously we described that flupirtine acts like an N-methyl-D-aspartate (NMDA) receptor antagonist in neuronal cells both in vitro and in vivo. Here we show that flupirtine displays its anti-apoptotic effect also in hNT (human Ntera/D1) neurons. hNT neurons were induced to apoptosis applying glutamate (Glu; at concentrations > or = 1 mM) or NMDA (> or = 1 mM). During Glu/NMDA-mediated apoptosis the levels of the intracellular anti-apoptotic agents Bc1-2 and glutathione dropped by more than 50%. Flupirtine completely abolished this reduction of Bc1-2 and glutathione leve…
Apaf-1 deficient mouse fibroblasts are resistant to MNNG and MMS-induced apoptotic death without attenuation of Bcl-2 decline.
2005
Abstract Simple alkylating agents induce cell death by activating the apoptotic pathway. In rodent fibroblasts, apoptosis triggered by DNA methylation lesions is executed via the mitochondrial damage pathway. Here, we studied cell death induced by the methylating agents methyl methanesulfonate (MMS) and N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) in mouse fibroblasts wild-type (wt) and deficient for Apaf-1 (apaf-1 knockout cells). Apaf-1 is an essential component of the apoptosome complex that becomes activated upon cytochrome c release from mitochondria. We show that apaf-1 knockout cells are more resistant to the cytotoxic effect (as measured by WST assay) of methylating agents. This is d…
Peptides in apoptosis research
2002
Apoptosis is a complex process that plays a central role in physiological and pathological cell death. This fast evolving research area has experienced incredible development in the past few years. Progress in the knowledge of the structure of many of the main molecular actors of the apoptotic signal transduction pathways has driven the design of synthetic peptides that in some cases can function as simplified versions of their parent proteins. These molecules are contributing to a better understanding of the activity and regulation of apoptotic proteins and also are setting the basis for the discovery of effective drugs to combat important diseases related to apoptosis. Most applications o…
Cameroonian Medicinal Plants: Pharmacology and Derived Natural Products
2010
Many developing countries including Cameroon have mortality patterns that reflect high levels of infectious diseases and the risk of death during pregnancy and childbirth, in addition to cancers, cardiovascular diseases and chronic respiratory diseases that account for most deaths in the developed world. Several medicinal plants are used traditionally for their treatment. In this review, plants used in Cameroonian traditional medicine with evidence for the activities of their crude extracts and/or derived products have been discussed. A considerable number of plant extracts and isolated compounds possess significant antimicrobial, anti-parasitic including antimalarial, anti-proliferative, a…
Effects of chemically modified tetracyclines (CMTs) in sensitive, multidrug resistant and apoptosis resistant leukaemia cell lines
2001
Recently discovered chemically modified tetracyclines (CMTs) have shown in vitro and in vivo anti-proliferative and anti-tumour activities. Here, we evaluated in vitro the anti-proliferative and apoptotic activity of six different dedimethylamino chemically modified tetracyclines (CMT-1, CMT-3, CMT-5, CMT-6, CMT-7 and CMT-8) in sensitive and multidrug resistant myeloid leukaemia cells (HL60 and HL60R) in vitro. Three of these compounds (CMT-5, CMT-6, CMT-7) showed low cytotoxic activity both in sensitive and in resistant cells, CMT-3 was endowed with a high anti-proliferative activity only in sensitive cells and was moderately effective as apoptosis inducing agent, with an activity similar …