Papers by Giuseppe Palumbo
Blood, 2019
BACKGROUND Multiple myeloma (MM) is a B-cell malignancy critically dependent for survival and pro... more BACKGROUND Multiple myeloma (MM) is a B-cell malignancy critically dependent for survival and proliferation on signals coming from its inflammatory microenvironment in which toll-like receptors (TLR) may be potential linking elements between inflammation and cancer. It has been recently demonstrated that TLR4 pathway provides a protective effect against bortezomib (BTZ)-induced endoplasmic reticulum (ER) stress and pre-treatment of MM cells with LPS significantly reduces BTZ-induced apoptosis. AIM Since the acquisition of BTZ resistance is accompanied by an increased reliance on mitochondrial respiration, we investigated the role of TLR4 as stress-responsive mechanism that protect mitochondria during BTZ-induced ER stress as potential mechanism of drug resistance. RESULTS The activation of TLR4 signaling by LPS increased mitochondrial mass in human MM cell lines (HMCL: U266, MM1.S, OPM2, NCI-H929) and induced up-regulation of mitochondrial biogenesis markers (PGC1a, PRC and TFAM). A...
International Journal of Molecular Sciences, 2015
Photofrin/photodynamic therapy (PDT) at sub-lethal doses induced a transient stall in proteasome ... more Photofrin/photodynamic therapy (PDT) at sub-lethal doses induced a transient stall in proteasome activity in surviving A549 (p53 +/+) and H1299 (p53 −/−) cells as indicated by the time-dependent decline/recovery of chymotrypsin-like activity. Indeed, within 3 h of incubation, Photofrin invaded the cytoplasm and localized preferentially within the mitochondria. Its light activation determined a decrease in mitochondrial membrane potential and a reversible arrest in proteasomal activity. A similar result is obtained by treating cells with Antimycin and Rotenone, indicating, as a common denominator of this effect, the ATP decrease. Both inhibitors, however, were more toxic to cells as the recovery of proteasomal activity was incomplete. We evaluated whether combining PDT (which is a treatment for killing tumor cells, per se, and inducing proteasome arrest in the surviving ones) with Bortezomib doses capable of sustaining the stall would protract the arrest with sufficient time to induce apoptosis in remaining cells.
Journal of the American College of Cardiology, 1995
Oxygen radicals may induce both peroxidation of polyunsaturated lipids and protein alterations in... more Oxygen radicals may induce both peroxidation of polyunsaturated lipids and protein alterations in low density lipoprotein (LDL). Oxidized LDL taken up by macrophages via the “scavenger” receptor may contribute to formation of foam cells. Previous studies have shown that β -blocker agents reduce experimental atherosclerosis in primates. In addition, we have previously shown that β -blocker agents inhibit oxygen radical-induced lipid peroxidation. Thus, in this study we have investigated whether β -blockers may prevent oxidative modifications induced by oxygen radicals on apolipoprotein-B 100 (apo-B 100 ) of LDL. Purified human LDL was exposed to oxygen radicals generated by CuSO 4 (15 μ M for 20 hs at 37° C) under control conditioincubation with propranolol (P: 1–10μmM). The index of peroxidation malonildihaldehyde, by thiobarbiturate method, was 2.1 ± 0.5* nmoles/mg of protein in native LDL, 34.5 ± 4.1 in control LDL and decreased to 6.5 ± 1.8* in LDL incubated with P (*p l 0.01 vs controls). When oxidized LDL was run on SDS-polyacrylamide electrophoresis (SDS-PAGE: 5 to 10% gradient) extensive apo-B 100 fragmentation was observed. Addition of P prevented the apo-B 100 fragmentation (mean reduction from 12 to 3 bands of low molecular weight). Moreover, oxidized LDL had increased mobility on 0.8% agarose gel electrophoresis (2.8 ± 0.4 time than controls). Similarly, incubation with P reduced LDL mobility to 0.8 ± 0.2 fold in respect to controls (p l 0.05). These data demostrate protection by propranonol on apo-B 100 oxidation in vitro, at clinically relevant concentrations. Although β -blockers are known to adversely affect lipid metabolism, inhibition of both LDL peroxidation and apo-B 100 fragmentation may reduce uptake of oxidized LDL by macrophages and hence foam cell formation.
Journal of Molecular and Cellular Cardiology, 1991
Molecules, 2016
The methanol extracts of the aerial part of four ethnomedicinal plants of Mediterranean region, t... more The methanol extracts of the aerial part of four ethnomedicinal plants of Mediterranean region, two non-seed vascular plants, Equisetum hyemale L. and Phyllitis scolopendrium (L.) Newman, and two Spermatophyta, Juniperus communis L. (J. communis) and Cotinus coggygria Scop. (C. coggygria), were screened against four human cells lines (A549, MCF7, TK6 and U937). Only the extracts of J. communis and C. coggygria showed marked cytotoxic effects, affecting both cell morphology and growth. A dose-dependent effect of these two extracts was also observed on the cell cycle distribution. Incubation of all the cell lines in a medium containing J. communis extract determined a remarkable accumulation of cells in the G2/M phase, whereas the C. coggygria extract induced a significant increase in the percentage of G1 cells. The novelty of our findings stands on the observation that the two extracts, consistently, elicited coherent effects on the cell cycle in four cell lines, independently from their phenotype, as two of them have epithelial origin and grow adherent and two are lymphoblastoid and grow in suspension. Even the expression profiles of several proteins regulating cell cycle progression and cell death were affected by both extracts. LC-MS investigation of methanol extract of C. coggygria led to the identification of twelve flavonoids (compounds 1-11, 19) and eight polyphenols derivatives (12-18, 20), while in J. communis extract, eight flavonoids (21-28), a α-ionone glycoside (29) and a lignin (30) were found. Although many of these compounds have interesting individual biological activities, their natural blends seem to exert specific effects on the proliferation of cell lines either growing adherent or in suspension, suggesting potential use in fighting cancer.
Medical Oncology, 2010
The debate about the health risks from low doses of radiation is vigorous and often acrimonious s... more The debate about the health risks from low doses of radiation is vigorous and often acrimonious since many years and does not appear to weaken. Being far from completeness, this review presents only a bird's eye view on current concepts and research in the field. It is organized and divided in two parts. The first is dedicated to molecular responses determined by radiation-induced DNA ruptures. It focuses its attention on molecular pathways that are activated by ATM and tries to describe the variegated functions and specific roles of Chk2 and p53 and other proteins in sensing, promoting and executing DNA repair. The second part is more concerned with the risk associated with exposure to low dose radiation and possible effects that the radiation-affected cell may undergo. These effects include induction of apoptosis and mitotic catastrophe, bystander effect and genomic instability, senescence and hormetic response. Current hypotheses and research on these issues are briefly discussed.
Biochemical and Biophysical Research Communications, Aug 14, 1992
Molecular Cancer Therapeutics, May 1, 2004
Objective: We investigated the effects of photodynamic therapy (PDT) combined with low-dose chemo... more Objective: We investigated the effects of photodynamic therapy (PDT) combined with low-dose chemotherapy on breast cancer cells. Photodynamic treatment was administered by irradiating indocyanine green-preloaded MCF-7 cells with an IR diode laser source at 805 nm; cisplatin was used for chemotherapy. Methods: The dose-response phenomena associated with the two treatments administered individually and together were evaluated with the following tests: trypan blue dye exclusion, 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay, clonogenic survival, thymidine and methionine incorporation, and insulin-dependent and insulin-independent glucose transport. Results: Viability and metabolic data demonstrated mutual reinforcement of therapeutic efficacy. However, isobolographic analysis of quantal and variable data indicated that reinforcement was additive according to trypan blue data and synergistic according to MTT data. To investigate the molecular mechanisms underlying alterations in cell proliferation and apoptosis, we evaluated (by Western blotting) the expression of proteins Bcl-2, Bax, Bcl-X L , p21, p53, and poly(ADP-ribose) polymerase. Photodynamic treatment caused transient selective destruction of Bcl-2 and up-regulation of Bax. It also induced apoptosis in a limited fraction of cells (10-12%). Flow cytometry data showed that PDT killed mostly G 1-phase cells, whereas cisplatin killed mostly S-phase cells. This disjointed phase-related effect may account for the favorable effects exerted by combined treatment. Conclusions: Our findings imply that low doses of cytostatic drugs may be as effective or even more effective than currently used doses if appropriately combined with PDT. [Mol Cancer Ther 2004;3(5):537-44]
Gynecologic Oncology, Nov 30, 1996
J Amer Coll Cardiol, 1995
Journal of Biological Chemistry
The effects of lysolecithin and hexadecyltrimethylammonium bromide on the structure and stability... more The effects of lysolecithin and hexadecyltrimethylammonium bromide on the structure and stability of apoA-II from human high density lipoprotein have been evalued by circular dichroism and fluorescence measurements. There is a profound enhancement in the stability of apoA-II to guanidinium hydrochloride denaturation when it forms a phospholipid complex with lysolecithin micelles. This complex is not only resistant to guanidinium hydrochloride denaturation, but it can be formed in a 6 M solution of this denaturant. The behavior of apoA-II in the native human high density protein is much closer to that of the lysolecithin apoA-II complex than to that of the free apoA-II.
International Journal of Molecular Sciences, 2015
Although photodynamic therapy (PDT), a therapeutic approach that involves a photosensitizer, ligh... more Although photodynamic therapy (PDT), a therapeutic approach that involves a photosensitizer, light and O2, has been principally considered for the treatment of specific types of cancers, other applications exist, including the treatment of infections. Unfortunately, PDT does not always guarantee full success since it exerts lethal effects only in cells that have taken up a sufficient amount of photosensitizer and have been exposed to adequate light doses, conditions that are not always achieved. Based on our previous experience on the combination PDT/chemotherapy, we have explored the possibility of fighting bacteria that commonly crowd infected surfaces by combining PDT with an antibiotic, which normally does not harm the strain at low concentrations. To this purpose, we employed 5-aminolevulinic acid (5-ALA), a pro-drug that, once absorbed by proliferating bacteria, is converted into the natural photosensitizer Protoporphyrin IX (PpIX), followed by Gentamicin. Photoactivation generates reactive oxygen species (ROS) which damage or kill the cell, while Gentamicin, even at low doses, ends the work. Our experiments, in combination, have been highly successful against biofilms produced by
Oxidative Medicine and Cellular Longevity, 2015
Heat shock 60 kDa protein 1 (HSP60) is a chaperone and stress response protein responsible for pr... more Heat shock 60 kDa protein 1 (HSP60) is a chaperone and stress response protein responsible for protein folding and delivery of endogenous peptides to antigen-presenting cells and also a target of autoimmunity implicated in the pathogenesis of atherosclerosis. By two-dimensional electrophoresis and mass spectrometry, we found that exposure of human promyelocytic HL-60 cells to a nontoxic concentration (10 μM) of 4-hydroxy-2-nonenal (HNE) yielded a HSP60 modified with HNE. We also detected adducts of HNE with putative uncharacterized protein CXorf49, the product of an open reading frame identified in various cell and tissue proteomes. Moreover, exposure of human monocytic THP-1 cells differentiated with phorbol 12-myristate 13-acetate to 10 μM HNE, and to light density lipoprotein modified with HNE (HNE-LDL) or by copper-catalyzed oxidation (oxLDL), but not to native LDL, stimulated the formation of HNE adducts with HSP60, as detected by immunoprecipitation and western blot, well over...
Cardiologia (Rome, Italy), 1994
Low-density lipoproteins (LDL) oxidized by oxygen radicals are a potent atherogenic stimulus. Che... more Low-density lipoproteins (LDL) oxidized by oxygen radicals are a potent atherogenic stimulus. Chemically modified LDL are internalized by macrophages via a specific cell surface receptor that was termed the scavenger receptor, and could induce foam cell transformation. Post-translational nonenzymatic glycosylation of low density lipoprotein (LDL) occurs in vivo in diabetic patients. Glycosylated LDL (glcLDL) is degraded by macrophages in part by the classic LDL-receptor and in part by the scavenger receptor. This latter mechanism may contribute to the formation of foam cells and acceleration of atherosclerosis in diabetes mellitus. Oxygen free radicals (ORs) could induce LDL peroxidation and subsequent formation of foam cells. Glycosylation may alter protein conformation. A free radical is any chemical species that has an unpaired electron. This property renders it highly chemically reactive. When a radical reacts with a non radical another free radical is generated. This characteri...
Lasers and Current Optical Techniques in Biology, 2004
Lasers and Current Optical Techniques in Biology, 2004
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Lasers and Current Optical Techniques in Biology, 2004
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Papers by Giuseppe Palumbo