Search results for "cancer cell"

PON3 is upregulated in cancer tissues and protects against mitochondrial superoxide-mediated cell death

2012

To achieve malignancy, cancer cells convert numerous signaling pathways, with evasion from cell death being a characteristic hallmark. The cell death machinery represents an anti-cancer target demanding constant identification of tumor-specific signaling molecules. Control of mitochondrial radical formation, particularly superoxide interconnects cell death signals with appropriate mechanistic execution. Superoxide is potentially damaging, but also triggers mitochondrial cytochrome c release. While paraoxonase (PON) enzymes are known to protect against cardiovascular diseases, recent data revealed that PON2 attenuated mitochondrial radical formation and execution of cell death. Another famil…

p53 as the main traffic controller of the cell signaling network

2010

Among different pathological conditions that affect human beings, cancer has received a great deal of attention primarily because it leads to significant morbidity and mortality. This is essentially due to increasing world-wide incidence of this disease and the inability to discover the cause and molecular mechanisms by which normal human cells acquire the characteristics that define cancer cells. Since the discovery of p53 over a quarter of a century ago, it is now recognized that virtually all cell fate pathways of live cells and the decision to die are under the control of p53. Such extensive involvement indicates that p53 protein is acting as a major traffic controller in the cell signa…

On Cancer Cell Cycle and Universal Apoptosis Parameters Signaling Unravelled In Silico

2010

Here, cell cycle in higher eukaryotes and their molecular networks signals both in G1/S and G2/M transitions are in silico replicated. Systems control theory is employed to design multi-nestled digital layers to simulate protein-toprotein activation and inhibition in the cancer cell cycle dynamics in presence of damaged genome. Sequencing and controlling the digital process of four micro-scale species networks (p53/Mdm2/DNA damage; p21mRNA/cyclin-CDK complex; CDK/CDC25/wee1/SKP2/APC/CKI and apoptosis target genes system) paved the way for unravelling the participants and their by-products having the task to execute (or not) cell death. The results of the proposed cell digital multi-layers g…

Biodistribution, Uptake and Effects Caused by Cancer-derived Extracellular Vesicles

2015

Extracellular vesicles (EVs) have recently emerged as important mediators of intercellular communication. They are released in the extracellular space by a variety of normal and cancerous cell types and have been found in all human body fluids. Cancer-derived EVs have been shown to carry lipids, proteins, mRNAs, non-coding and structural RNAs and even extra-chromosomal DNA, which can be taken up by recipient cells and trigger diverse physiological and pathological responses. An increasing body of evidence suggests that cancer-derived EVs mediate paracrine signalling between cancer cells. This leads to the increased invasiveness, proliferation rate and chemoresistance, as well as the acquisi…

Melanoma-Reactive Class I-Restricted Cytotoxic T Cell Clones Are Stimulated by Dendritic Cells Loaded with Synthetic Peptides, but Fail to Respond to…

2003

Abstract Immunization with heat shock proteins (hsp) isolated from cancer cells has been shown to induce a protective antitumor response. The mechanism of hsp-dependent cellular immunity has been attributed to a variety of immunological activities mediated by hsp. Hsp have been shown to bind antigenic peptides, trim the bound peptides by intrinsic enzymatic activity, improve endocytosis of the chaperoned peptides by APCs, and enhance the ability of APCs to stimulate peptide-specific T cells. We have investigated the potential capacity of hsp70 and gp96 to function as a mediator for Ag-specific CTL stimulation in an in vitro model for human melanoma. Repetitive stimulation of PBLs by autolog…

Cytotoxicity of two naturally occurring flavonoids (dorsmanin F and poinsettifolin B) towards multi-factorial drug-resistant cancer cells.

2015

Abstract Introduction The expression of diverse resistance mechanisms in cancer cells is one of the major barriers to successful cancer chemotherapy. Methods In the present study, we assessed the cytotoxicity of two naturally occurring flavonoids dorsmanin F ( 1 , a flavanone) and poinsettifolin B ( 2 , a chalcone) against 9 drug-sensitive and multidrug-resistant (MDR) cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were all analysed via flow cytometry. Results Compounds 1 and…

Cytotoxicity of three naturally occurring flavonoid derived compounds (artocarpesin, cycloartocarpesin and isobavachalcone) towards multi-factorial d…

2015

Abstract Introduction Cancer remains an aggressive deadly disease, if drug resistance develops. This problem is aggravated by the fact that multiple rather than single mechanisms are involved in resistance and that multidrug resistance (MDR) phenomena cause inefficacy of many clinical established anticancer drugs. We are seeking for novel cytotoxic phytochemicals to combat drug-resistant tumour cells. Methods In the present study, we investigated the cytotoxicity of three naturally occurring flavonoids including two flavones artocarpesin (1) and cycloartocarpesin (2) and one chalcone, isobavachalcone (3) against 9 drug-sensitive and MDR cancer cell lines. The resazurin reduction assay was u…

Liquid Biopsy in Cancer Patients: The Hand Lens to Investigate Tumor Evolution

2017

In recent years the treatment of cancer patients has profoundly changed due to a better comprehension of the biological processes underlying tumor development and progression. Several tumors are defined as “oncogene addicted” and this discovery has led the way to the development of target therapies that are able to specifically kill cancer cells sparing normal cells from toxicity. Nowadays treatment decision is strictly dependent on the molecular characterization of the tumor; thus the path of cancer patients’ survival is tissue dependent but this may have several limitations. Indeed a single tissue biopsy represents only a snapshot limited in time and space but we are learning that tumor e…

FT-IR spectroscopy studies of the breast cancer cell composition changes induced by Au-BSA nanoclusters

2016

Polyaminoacid–doxorubicin prodrug micelles as highly selective therapeutics for targeted cancer therapy

2016

An amphiphilic copolymer carrying high-dose doxorubicin (21% on a weight basis), PHEA–EDA–P,C–Doxo, was prepared by coupling doxorubicin with a biocompatible polyaminoacid through a pH-sensitive spacer. Additional derivatization with 4-pentynoic acid endows it with self-assembling properties by means of π–π stacking. These micelles can be triggered to promptly release drug in lysosomes (∼40% in 12 h) through pH-dependent micelle hydrolysis after uptake. In vitro tests on co-cultures of cancer (MDA-MB 231) and normal (HB-2) breast cells proved that the conjugate was selectively internalized into the former rather than normal cells, exploiting the caveolae-dependent endocytosis pathway, expla…