Search results for "Cell death"

Melatonin induces transcriptional regulation of Bim by FoxO3a in HepG2 cells

2012

Background: Melatonin induces apoptosis in many different cancer cell lines, including hepatocellular carcinoma cells. However, the responsible pathways have not been clearly elucidated. A member of the forkhead transcription factors' family, FoxO3a, has been implicated in the expression of the proapoptotic protein Bim (a Bcl-2-interacting mediator of cell death). In this study, we used human HepG2 liver cancer cells as an in vitro model to investigate whether melatonin treatment induces Bim through regulation by the transcription factor FoxO3a. Methods: Cytotoxicity of melatonin was compared in HepG2 hepatoblastoma cells and primary human hepatocytes. Proapoptotic Bim expression was analys…

Nerve growth factor and epidermal growth factor stimulate clusterin gene expression in PC12 cells

1999

Clusterin (apolipoprotein J) is an extracellular glycoprotein that might exert functions in development, cell death and lipid transport. Clusterin gene expression is elevated at sites of tissue remodelling, such as differentiation and apoptosis; however, the signals responsible for this regulation have not been identified. We use here the clusterin gene as a model system to examine expression in PC12 cells under the control of differentiation and proliferation signals produced by nerve growth factor (NGF) and by epidermal growth factor (EGF) respectively. NGF induced clusterin mRNA, which preceded neurite outgrowth typical of neuronal differentiation. EGF also activated the clusterin mRNA, …

Heterocycle-containing retinoids. Discovery of a novel isoxazole arotinoid possessing potent apoptotic activity in multidrug and drug-induced apoptos…

2001

In a search for retinoic acid (RA) receptor ligands endowed with potent apoptotic activity, a series of novel arotinoids were prepared. Because the stereochemistry of the C9-alkenyl portion of natural 9-cis-RA and the olefinic moiety of the previously synthesized isoxazole retinoid 4 seems to have particular importance for their apoptotic activity, novel retinoid analogues with a restricted or, vice versa, a larger flexibility in this region were designed and prepared. The new compounds were evaluated in vitro for their ability to activate natural retinoid receptors and for their differentiation-inducing activity. Cytotoxic and apoptotic activities were, in addition, evaluated. In general, …

Plasmodium falciparumMalaria: Reduction of Endothelial Cell Apoptosis In Vitro

2005

ABSTRACTOrgan failure inPlasmodium falciparummalaria is associated with neutrophil activation and endothelial damage. This study investigates whether neutrophil-induced endothelial damage involves apoptosis and whether it can be prevented by neutralization of neutrophil secretory products. Endothelial cells from human umbilical veins were coincubated with neutrophils from healthy donors and with sera from eight patients withP. falciparummalaria, three patients withP. vivaxmalaria, and three healthy controls. Endothelial apoptosis was demonstrated by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) and annexin V staining. The rate of apoptosis of cells was …

Molecular docking and pharmacogenomics of vinca alkaloids and their monomeric precursors, vindoline and catharanthine.

2011

International audience; Vinblastine and vincristine are dimeric indole alkaloids derived from (formerly: ). Their monomeric precursor molecules are vindoline and catharanthine. While vinblastine and vincristine are well-known mitotic spindle poisons, not much is known about vindoline and catharanthine. Vindoline and catharanthine showed weak cytotoxicity, while vinblastine, vincristine, and the semisynthetic vindesine and vinorelbine revealed high cytotoxicity towards cancer cells. This may reflect a general biological principle of poisonous plants. Highly toxic compounds are not only active towards predators, but also towards plant tissues. Hence, plants need mechanisms to protect themselv…

Hypoxia Positively Regulates the Expression of pH-Sensing G-Protein–Coupled Receptor OGR1 (GPR68)

2016

Background & Aims: A novel family of proton-sensing G-proteinâcoupled receptors, including ovarian cancer G-proteinâcoupled receptor 1 (OGR1) (GPR68) has been identified to play a role in pH homeostasis. Hypoxia is known to change tissue pH as a result of anaerobic glucose metabolism through the stabilization of hypoxia-inducible factor-1α. We investigated how hypoxia regulates the expression of OGR1 in the intestinal mucosa and associated cells. Methods: OGR1 expression in murine tumors, human colonic tissue, and myeloid cells was determined by quantitative reverse-transcription polymerase chain reaction. The influence of hypoxia on OGR1 expression was studied in monocytes/macrophages and…

Depletion ofL-arginine induces autophagy as a cytoprotective response to endoplasmic reticulum stress in human T lymphocytes

2012

PMCID: PMC3494587

Targeting NUPR1 with the Small Compound ZZW-115 Is an Efficient Strategy to Treat Hepatocellular Carcinoma

2020

International audience; HCC is a highly lethal malignancy with Sorafenib as the only molecularly targeted drug. The multifunctional stress-associated protein, NUPR1, plays an essential role in controlling cell growth, migration, invasion and Sorafenib resistance in HCC. We report here that NUPR1 expression is absent in healthy liver and it is progressively upregulated in HCC premalignant lesions such as hepatitis and cirrhosis with a maximum expression in HCC samples, highlighting that NUPR1 is a potential drug target for HCC. We therefore assessed in this work, ZZW-115, a strong inhibitor of NUPR1, as a promising candidate for the treatment of HCC. We validated its extraordinary antitumor …

Knowledge-based strategy to trigger grapevine immunity

2012

The multiple facets of Cajal-Retzius neurons.

2021

ABSTRACTCajal-Retzius neurons (CRs) are among the first-born neurons in the developing cortex of reptiles, birds and mammals, including humans. The peculiarity of CRs lies in the fact they are initially embedded into the immature neuronal network before being almost completely eliminated by cell death at the end of cortical development. CRs are best known for controlling the migration of glutamatergic neurons and the formation of cortical layers through the secretion of the glycoprotein reelin. However, they have been shown to play numerous additional key roles at many steps of cortical development, spanning from patterning and sizing functional areas to synaptogenesis. The use of genetic l…