Giuseppe Filomeni | "Tor Vergata" University of Rome (original) (raw)

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Papers by Giuseppe Filomeni

Free Radical Research, 2007

In this study, we found that production of both reactive oxygen (ROS) and nitrogen (RNS) species ... more In this study, we found that production of both reactive oxygen (ROS) and nitrogen (RNS) species is a very early event related to treatment with hyperosmotic concentration of sorbitol. The production of nitric oxide (NO) was paralleled by the increase of the mRNA and protein level of the inducible form of the nitric oxide synthase (iNOS). ROS and RNS enhancement, process concomitant to the failure of mitochondrial trans-membrane potential (DeltaPsi), was necessary for the induction of apoptosis as demonstrated by the protection against sorbitol-mediated toxicity observed after treatment with ROS scavengers or NOS inhibitors. The synergistic action of ROS and RNS was finally demonstrated by pre-treatment with rosmarinic acid that, by powerfully buffering both these species, prevents impairment of DeltaPsi and cell death. Overall results suggest that the occurrence of apoptosis upon sorbitol treatment is an event mediated by oxidative/nitrosative stress rather than a canonical hyperosmotic shock.

Selected 7-nitro-2,1,3-benzoxadiazole derivatives have been recently found very efficient inhibit... more Selected 7-nitro-2,1,3-benzoxadiazole derivatives have been recently found very efficient inhibitors of glutathione S- transferase (GST) P1-1,5 an enzyme which displays antiapop- totic activity and is also involved in the cellular resistance to anticancer drugs. These new inhibitors are not tripeptide glutathione-peptidomimetic molecules and display lipophylic properties suitable for crossing the plasma membrane. In the present work, we show the strong

Cancer research, 2005

... the almost undetectable levels of GPx measured in other cell types (eg, neuroblastoma SH-SY5Y... more ... the almost undetectable levels of GPx measured in other cell types (eg, neuroblastoma SH-SY5Y cells; data ... of ASK1-mediated signal transduction in oxidative stress-and endoplasmic reticulum stress-induced apoptosis: advanced findings from ASK1 knockout mice. ...

Glutathione and Sulfur …, 2009

... AND APOPTOSIS GIUSEPPE FILOMENI, KATIA AQUILANO, and MARIA ROSA CIRIOLO 10.1 INTRODUCTION ...... more ... AND APOPTOSIS GIUSEPPE FILOMENI, KATIA AQUILANO, and MARIA ROSA CIRIOLO 10.1 INTRODUCTION ... Glutathione and Sulfur Amino Acids in Human Health and Disease. Edited by R. Masella and G. Mazza Copyright © 2009 John Wiley & Sons, Inc. 211 Page 2. ...

We have previously characterized the cytotoxic action of diallyl disulfide (DADS) on neuroblastom... more We have previously characterized the cytotoxic action of diallyl disulfide (DADS) on neuroblastoma cells, and we have shown the crucial role of an early and massive reactive oxygen species production in the induction of c-Jun NH2-terminal kinase-mediated apoptotic pathway. In the present work, we report that DADS is ineffective in inducing apoptosis in a human adenocarcinoma gastric cell line (AGS).

The Journal of biological chemistry, Jan 20, 2007

We characterized the pro-apoptotic activity of two new synthesized isatin-Schiff base copper(II) ... more We characterized the pro-apoptotic activity of two new synthesized isatin-Schiff base copper(II) complexes, obtained from isatin and 1,3-diaminopropane or 2-(2-aminoethyl)pyridine: (Cu(isapn)) and (Cu(isaepy)(2)), respectively. We demonstrated that these compounds trigger apoptosis via the mitochondrial pathway. The early induction of the p53/p21 system indicates a role for p53 in cell death, however, experiments carried out with small interfering RNA against p53, or with cells lacking p53, support that a p53-independent mechanism can also occur. The extent of apoptosis mirrors the kinetics of intracellular copper uptake. Particularly, Cu(isaepy)(2) enters the cells more efficiently and specifically damages nuclei and mitochondria, as evidenced by atomic absorption analysis of copper content and by the extent of nuclear and mitochondrial integrity. Conversely, Cu(isapn), although less permeable, induces a wide-spread oxidative stress, as demonstrated by analyses of reactive oxygen s...

Cancer research, Jan 15, 2003

The pharmacological properties of garlic and its derivatives are long known, and their underling ... more The pharmacological properties of garlic and its derivatives are long known, and their underling mechanisms are being extensively investigated. In this study we have addressed the effects of diallyl disulfide (DADS), an oil-soluble garlic molecule, on cell growth of neuroblastoma cell SH-SY5Y, focusing on the redox events associated with this compound. Treatment of SH-SY5Y cells with DADS resulted in arrest of cell cycle in G(2)/M phase and commitment to apoptosis through the activation of the mitochondrial pathway (Bcl-2 down-regulation, cytochrome c release into the cytosol, and activation of caspase-9 and caspase-3). The earliest oxidative event observed after DADS treatment was the increase of production of reactive oxygen species, which reached the maximum yield on 30 min of DADS treatment. The oxidative burst resulted in protein and lipid damage as demonstrated by protein carbonyl accumulation and lipid peroxidation. We demonstrated that apoptosis induction was highly dependen...

Autophagy, 2010

Kaempferol, a dietary cancer chemopreventive polyphenol, has been reported to trigger apoptosis i... more Kaempferol, a dietary cancer chemopreventive polyphenol, has been reported to trigger apoptosis in several tumor histotypes, but the mechanism underlying this phenomenon is not fully understood. Here, we demonstrate that in HeLa cells, kaempferol induces energetic failure due to inhibition of both glucose uptake and Complex I of the mitochondrial respiratory chain. As adaptive response, cells activate autophagy, the occurrence of which was established cytofluorometrically, upon acridine orange staining, and immunochemically, by following the increase of the autolysosome-associated form of the microtubule-associated protein light chain 3 (LC3-II). Autophagy is an early and reversible process occurring as survival mechanisms against apoptosis. Indeed, chemical inhibition of autophagy, by incubations with monensin, wortmannin, 3-methyladenine, or by silencing Atg5, significantly increases the extent of apoptosis, which takes place via the mitochondrial pathway, and shortens the time in...

The Journal of nutrition, 2008

Much evidence in the last few years suggests that the antiproliferative effects of various garlic... more Much evidence in the last few years suggests that the antiproliferative effects of various garlic secondary metabolites in in vitro experimental systems are due to redox-based mechanisms. In particular, sulfur-containing allyl compounds have been demonstrated to generate reactive oxygen species and to modify directly the redox state of specific reactive cysteines on protein surfaces. On the basis of such properties, allyl compounds, in particular the ones present in the oil-soluble fraction of garlic extracts, can function as modulators of several redox-mediated signaling pathways related to the activation of mitogen-activated protein kinases, cell cycle, DNA repair, and cell demise. However, even though many in vitro studies have tried to dissect the mechanisms of action of garlic derivatives, research in this field is still incomplete and questions about bioavailability, biotransformation, and pro-oxidant activity are still unanswered. This review discusses recent findings on such...

International journal of cell biology, 2012