MDL 72527 and spermine oxidation products induce a lysosomotropic effect and mitochondrial alterations in tumour cells

2007 ◽  
Vol 35 (2) ◽  
pp. 343-348 ◽  
Author(s):  
E. Agostinelli ◽  
G. Tempera ◽  
L. Dalla Vedova ◽  
M. Condello ◽  
G. Arancia
Keyword(s):  
Amine Oxidase ◽  
Colon Adenocarcinoma ◽  
Multidrug Resistant ◽  
Oxidation Products ◽  
Mitochondrial Activity ◽  
Mitochondrial Alterations ◽  
Transmission Electron ◽  
Catalysed Oxidation ◽  
Mitochondrial Membrane Depolarization ◽  
Mdl 72527

Cytotoxic products of polyamines generated in situ by an enzyme-catalysed reaction may be useful as a new avenue in combating cancer. This study demonstrated that MDR (multidrug-resistant) cancer cells (colon adenocarcinoma and melanoma) are significantly more sensitive than the corresponding WT (wild-type) ones to H2O2 and aldehydes, the products of BSAO (bovine serum amine oxidase)-catalysed oxidation of spermine. Moreover, cytotoxicity was considerably greater when the treatment was carried out at 42°C than at 37°C. TEM (transmission electron microscopy) observations showed major ultrastructural alterations of the mitochondria. These were more pronounced in MDR than in WT cells. After treatment with BSAO/spermine, a higher mitochondrial membrane depolarization and an increased mitochondrial activity in drug-resistant cells were observed.

scholarly journals Spermine Oxidation Products Induce Mitochondrial Alterations on Tumor Cells

2012 ◽  
Vol 29 (3) ◽  
pp. 111-116
Author(s):  
Enzo Agostinelli
Keyword(s):  
Tumor Cells ◽  
Amine Oxidase ◽  
Apoptotic Cell ◽  
Colon Adenocarcinoma ◽  
Multidrug Resistant ◽  
Oxidation Products ◽  
Cytotoxic Agents ◽  
Mitochondrial Activity ◽  
Mitochondrial Alterations ◽  
Mitochondrial Membrane Depolarization

Spermine Oxidation Products Induce Mitochondrial Alterations on Tumor Cells Cytotoxic products of polyamines generated in situ by an enzyme-catalyzed reaction may be useful as a new avenue in combating cancer. This study demonstrates that multidrug resistant (MDR) cancer cells (colon adenocarcinoma and melanoma) are significantly more sensitive than the corresponding wild type (WT) ones to hydrogen peroxide and aldehydes, the products of bovine serum amine oxidase (BSAO)-catalyzed oxidation of spermine. Transmission electron microscopy (TEM) observations showed the major ultrastructural alterations of the mitochondria. These were more pronounced in MDR than in WT cells. After treatment with BSAO/spermine a higher mitochondrial membrane depolarization and an increased mitochondrial activity in drug-resistant cells were observed. The results suggest that enzymatically formed cytotoxic agents activate stress signal transduction pathways, leading to apoptotic cell death, mainly in multidrug resistant cell lines.

scholarly journals MDL 72527 and spermine oxidation products induce a lysosomotropic effect and mitochondrial alterations in tumour cells

2013 ◽  
Vol 41 (6) ◽  
pp. 1773-1773
Author(s):  
Enzo Agostinelli ◽  
Giampiero Tempera ◽  
Laura Dalla Vedova ◽  
Maria Condello ◽  
Giuseppe Arancia
Keyword(s):  
Tumour Cells ◽  
Oxidation Products ◽  
Mitochondrial Alterations ◽  
Mdl 72527

Mitochondrial alterations induced by serum amine oxidase and spermine on human multidrug resistant tumor cells

Amino Acids ◽  
2003 ◽  
Vol 26 (3) ◽  
Author(s):  
G. Arancia ◽  
A. Calcabrini ◽  
M. Marra ◽  
P. Crateri ◽  
M. Artico ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Amine Oxidase ◽  
Multidrug Resistant ◽  
Mitochondrial Alterations

Amine oxidase, spermine, and hyperthermia induce cytotoxicity in P-glycoprotein overexpressing multidrug resistant Chinese hamster ovary cells

2001 ◽  
Vol 79 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Stephanie Lord-Fontaine ◽  
Enzo Agostinelli ◽  
Ewa Przybytkowski ◽  
Diana A Averill-Bates
Keyword(s):  
Multidrug Resistance ◽  
Chinese Hamster Ovary ◽  
Amine Oxidase ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Multidrug Resistant ◽  
Oxidation Products ◽  
Glutathione S Transferase ◽  
Ovary Cells ◽  
P Glycoprotein

Multidrug resistance is a major obstacle for the successful use of chemotherapy. The multidrug resistance phenotype is often attributed to overexpression of P-glycoprotein, which is an energy-dependent drug efflux pump. We investigated a new strategy to overcome multidrug resistance, using purified bovine serum amine oxidase, which generates two major toxic products from the polyamine spermine. The cytotoxicity of the aldehyde(s) and H2O2, produced by the enzymatic oxidation of micromolar concentrations of spermine, was evaluated in multidrug resistant Chinese hamster ovary cells CHRC5 with overexpression of P-glycoprotein, using a clonogenic cell survival assay. We examined the ability of hyperthermia (42°C), and inhibition of cellular detoxification systems, to sensitize multidrug resistant cells to spermine oxidation products. Severe depletion of intracellular glutathione was achieved using L-buthionine sulfoximine and inhibition of glutathione S-transferase by ethacrynic acid. CHRC5 cells showed no resistance to the toxic oxidation products of spermine, relative to drug-sensitive AuxB1 cells. Exogenous catalase protected cells against cytotoxicity of H2O2, but spermine-derived aldehyde(s) still caused some cytotoxicity. Hyperthermia (42°C) enhanced cytotoxicity of spermine oxidation products. Cytotoxic responses in CHRC5 cells were compared to the drug-sensitive cells, to determine whether there are differential responses. CHRC5 cells were more sensitive to the cytotoxic effect of spermine oxidation products under more extreme conditions (higher temperature, higher spermine concentration, and longer exposure time). Glutathione depletion or glutathione S-transferase inhibition also led to enhanced cytotoxicity of spermine oxidation products in CHRC5 and AuxB1 cells. Our findings suggest that hyperthermia, combined with toxic oxidation products generated from spermine and amine oxidase, could be useful for eliminating drug-sensitive and multidrug resistant cells.Key words: amine oxidase, spermine, multidrug resistance, P-glycoprotein, hyperthermia.

scholarly journals In vitro biological activity of Hydroclathrus clathratus and its use as an extracellular bioreductant for silver nanoparticle formation

2020 ◽  
Vol 9 (1) ◽  
pp. 416-428 ◽  
Author(s):  
Raghad R. Alzahrani ◽  
Manal M. Alkhulaifi ◽  
Nouf M. Al-Enazi
Keyword(s):  
Biological Activity ◽  
Unsaturated Fatty Acids ◽  
Multidrug Resistant ◽  
Chemical Components ◽  
Resistant Bacteria ◽  
Transmission Electron ◽  
Hydroclathrus Clathratus ◽  
Adaptive Nature ◽  
First Time

AbstractThe adaptive nature of algae results in producing unique chemical components that are gaining attention due to their efficiency in many fields and abundance. In this study, we screened the phytochemicals from the brown alga Hydroclathrus clathratus and tested its ability to produce silver nanoparticles (AgNPs) extracellularly for the first time. Lastly, we investigated its biological activity against a variety of bacteria. The biosynthesized nanoparticles were characterized by UV-visible spectroscopy, Fourier-transform infrared spectroscopy, dynamic light scattering, transmission electron microscopy, and energy-dispersive spectroscopy. The biological efficacy of AgNPs was tested against eighteen different bacteria, including seven multidrug-resistant bacteria. Phytochemical screening of the alga revealed the presence of saturated and unsaturated fatty acids, sugars, carboxylic acid derivatives, triterpenoids, steroids, and other components. Formed AgNPs were stable and ranged in size between 7 and 83 nm and presented a variety of shapes. Acinetobacter baumannii, Staphylococcus aureus, Methicillin-resistant S. aureus (MRSA), and MDR A. baumannii were the most affected among the bacteria. The biofilm formation and development assay presented a noteworthy activity against MRSA, with an inhibition percentage of 99%. Acknowledging the future of nano-antibiotics encourages scientists to explore and enhance their potency, notably if they were obtained using green, rapid, and efficient methods.

scholarly journals The Synergistic Effect of Biosynthesized Silver Nanoparticles and Phage ZCSE2 as a Novel Approach to Combat Multidrug-Resistant Salmonella enterica

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 678
Author(s):  
Abdallah S. Abdelsattar ◽  
Rana Nofal ◽  
Salsabil Makky ◽  
Anan Safwat ◽  
Amera Taha ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Color Change ◽  
Antibacterial Properties ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Mortality And Morbidity ◽  
Novel Approach ◽  
Transmission Electron

The emergence and evolution of antibiotic-resistant bacteria is considered a public health concern. Salmonella is one of the most common pathogens that cause high mortality and morbidity rates in humans, animals, and poultry annually. In this work, we developed a combination of silver nanoparticles (AgNPs) with bacteriophage (phage) as an antimicrobial agent to control microbial growth. The synthesized AgNPs with propolis were characterized by testing their color change from transparent to deep brown by transmission electron microscopy (TEM) and Fourier-Transform Infrared Spectroscopy (FTIR). The phage ZCSE2 was found to be stable when combined with AgNPs. Both minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated for AgNPs, phage, and their combination. The results indicated that MIC and MBC values were equal to 23 µg/mL against Salmonella bacteria at a concentration of 107 CFU/mL. The combination of 0.4× MIC from AgNPs and phage with Multiplicity of Infection (MOI) 0.1 showed an inhibitory effect. This combination of AgNPs and phage offers a prospect of nanoparticles with significantly enhanced antibacterial properties and therapeutic performance.

scholarly journals A REVIEW: A GREEN APPROACH FOR THE SYNTHESIS OF SILVER NANOPARTICLES AND ITS ANTIBACTERIAL APPLICATIONS

2018 ◽  
Vol 11 (8) ◽  
pp. 74 ◽  
Author(s):  
Shyla Marjorie Haqq ◽  
Amit Chattree
Keyword(s):  
Silver Nanoparticles ◽  
Antimicrobial Properties ◽  
Nanoparticle Synthesis ◽  
Silver Ions ◽  
Multidrug Resistant ◽  
X Ray Diffraction ◽  
Green Approach ◽  
Transmission Electron ◽  
Uv Visible ◽  
Silver Nanoparticle Synthesis

  This review is based on the synthesis of silver nanoparticles (AgNPs) using a green approach which is biofabricated from various medicinal plants. AgNPs were prepared from the various parts of the plants such as the flowers, stems, leaves, and fruits. Various physiochemical characterizations were performed using the ultraviolet (UV)-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction spectroscopy, transmission electron microscopy, and energy dispersive spectroscopy. AgNPs were also used to inhibit the growth of bacterial pathogens and were found to be effective against both the Gram-positive and Gram-negative bacteria. For the silver to have antimicrobial properties, it must be present in the ionized form. All the forms of silver-containing compounds with the observed antimicrobial properties are in one way or another source of silver ions. Although the antimicrobial properties of silver have been known, it is thought that the silver atoms bind to the thiol groups in enzymes and subsequently leads to the deactivation of enzymes. For the silver to have antimicrobial properties, it must be present in the ionized form. The study suggested that the action of the AgNPs on the microbial cells resulted into cell lysis and DNA damage. AgNPs have proved their candidature as a potential antibacterial against the multidrug-resistant microbes. The biological agents for synthesizing AgNPs cover compounds produced naturally in microbes and plants. Reaction parameters under which the AgNPs were being synthesized hold prominent impact on their size, shape, and application. Silver nanoparticle synthesis and their application are summarized and critically discussed in this review.

Exploring the Contribution of Mycobacteria Characteristics in Their Interaction with Human Macrophages

2013 ◽  
Vol 19 (5) ◽  
pp. 1159-1169 ◽  
Author(s):  
Carla Silva ◽  
Joao Perdigao ◽  
Elsa Alverca ◽  
António P. Alves de Matos ◽  
Patricia A. Carvalho ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Envelope ◽  
Treatment Strategies ◽  
Human Monocyte ◽  
Selective Advantage ◽  
Multidrug Resistant ◽  
Structural Features ◽  
Major Health Problem ◽  
Transmission Electron ◽  
Mdr Tb

AbstractTuberculosis (TB) is a major health problem. The emergence of multidrug resistant (MDR)Mycobacterium tuberculosis(Mtb) isolates confounds treatment strategies. In Portugal, cases of MDR-TB are reported annually with an increased incidence noted in Lisbon. The majority of these MDR-TB cases are due to closely related mycobacteria known collectively as theLisboafamily and Q1 cluster. Genetic determinants linked to drug resistance have been exhaustively studied resulting in the identification of family and cluster specific mutations. Nevertheless, little is known about other factors involved in development of mycobacteria drug resistance. Here, we complement genetic analysis with the study of morphological and structural features of theLisboafamily and Q1 cluster isolates by using scanning and transmission electron microscopy. This analysis allowed the identification of structural differences, such as cell envelope thickness, between Mtb clinical isolates that are correlated with antibiotic resistance. The infection of human monocyte derived macrophages allowed us to document the relative selective advantage of theLisboafamily isolates over other circulating Mtb isolates.

Mitochondrial dysfunction is an early event in high-NaCl-induced apoptosis of mIMCD3 cells

2002 ◽  
Vol 282 (6) ◽  
pp. F981-F990 ◽  
Author(s):  
Luis Michea ◽  
Christian Combs ◽  
Peter Andrews ◽  
Natalia Dmitrieva ◽  
Maurice B. Burg
Keyword(s):  
Mitochondrial Dysfunction ◽  
Collecting Duct ◽  
Early Event ◽  
Mitochondrial Morphology ◽  
Cytochrome C Release ◽  
Activity Increase ◽  
Transmission Electron ◽  
Mitochondrial Membrane Depolarization ◽  
Medullary Collecting Duct ◽  
Induced Apoptosis

Raising osmolality to 700 mosmol/kgH2O by the addition of NaCl rapidly kills most murine inner renal medullary collecting duct cells (mIMCD3), but they survive at 500 mosmol/kgH2O. At 300 and 500 mosmol/kgH2O, NADH autofluorescence is present in a mitochondria-associated, punctate perinuclear pattern. Within 45 s to 30 min at 700 mosmol/kgH2O, the autofluorescence spreads diffusely throughout the cell. This correlates with mitochondrial membrane depolarization, measured as decreased tetramethylrhodamine methyl ester perchlorate (TMRM) fluorescence. Mitochondrial dysfunction should increase the cellular ADP/ATP ratio. In agreement, this ratio increases within 1–6 h. Mitochondrial morphology (transmission electron microscopy) is unaffected, but nuclear hypercondensation becomes evident. Progressive apoptosis occurs beginning 1 h after osmolality is raised to 700, but not to 500, mosmol/kgH2O. General caspase activity and caspase-9 activity increase only after 6 h at 700 mosmol/kgH2O. The mitochondrial Bcl-2/Bax ratio decreases within 1–3 h, but no cytochrome c release is evident. The mitochondria contain little p53 at any osmolality. Adding urea to 700 mosmol/kgH2O does not change NADH or TMRM fluorescence. We conclude that extreme acute hypertonicity causes a mitochondrial dysfunction involved in the initiation of apoptosis.

Sign in / Sign up

Export Citation Format

Share Document