Direct oxidative DNA damage, apoptosis and radio sensitivity by spermine oxidase activities in mouse neuroblastoma cells

Amendola, Roberto; Bellini, A.; Cervelli, Manuela; Degan, Paolo; Marcocci, Lucia; Martini, Federico; Mariottini, Paolo

doi:10.1016/j.bbcan.2005.02.002

Cited by 24 publications

(35 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Upon 2-and 4-Gy doses of X-irradiation, SMOX transfected cells were sensitized and more prone to die than mock transfected cells. Treatments with increasing doses of MDL abolished such radiosensitive predisposition (15,16). However, the level of X-ray delivered has to be considered as high doses, thus belonging to the LNT (linear no-threshold) theory of a linear dose-response.…”

Section: Msmox Radiation and Ros In A Neuroblastoma Cell Linementioning

confidence: 99%

“…The interconversion metabolism of SPM by SMOX produces hydrogen-peroxide and substantial evidence has addressed this fundamental aspect of SMOX activity to cause intracellular ROS (14)(15)(16). In Fig.…”

Section: Msmox and Ros In Aa8 Parental Ber Deficient Em9 And Ner Defmentioning

confidence: 99%

“…Increasing interest has been posed on the SPM amino oxidase (SMOX) and BSAO enzyme activities, since SPM catabolic degradation has been found closely related to DNA oxidation and apoptosis, mainly via hydrogen peroxide (H 2 O 2 ) production (12)(13)(14)(15). High SMOX activity provokes low level of SPM and the inhibition of the interactions with DNA, thus causing sensitivity to ionizing radiation exposure and cell death (15,16 (13,20) and in vivo many tumors appear resistant to oxidative stress and apoptosis, we dissected the influence of chronic sub-lethal DNA damage and DNA repair by mSMOX ectopically overexpressed in proficient Chinese hamster AA8 cell line and both deficient base-excision-repair (BER) EM9 (21) and transcriptioncoupled nucleotide-excision-repair (NER) UV61 (22) cell lines to represent cellular models of priming damage dose of ROS. Low doses of X-irradiation delivers challenging dose of damage evaluated at 6 and 24 h after exposure.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Reactive oxygen species spermine metabolites generated from amine oxidases and radiation represent a therapeutic gain in cancer treatments

Amendola

Cervelli

Fratini

et al. 2013

International Journal of Oncology

View full text Add to dashboard Cite

Abstract.The most frequent interventions in cancer therapy are currently the destruction of cells by irradiation or administration of drugs both able to induce radical formation and toxic metabolites by enzyme-catalyzed reactions. The aim of this study was to determine the cell viability of cells undergoing a DNA damage threshold accomplished by ROS overproduction via both ectopic expression of murine spermine oxidase (mSMOX) and bovine serum amine oxidase (BSAO) enzymes. Low dose of X-irradiation delivers a challenging dose of damage as evaluated in proficient Chinese hamster AA8 cell line and both deficient transcription-coupled nucleotide excision repair (NER) UV61 cells and deficient base excision repair (BER) EM9 cells, at 6 and 24 h after exposure. The priming dose of ROS overexposure by mSMOX provokes an adaptive response in N18TG2, AA8 and EM9 cell lines at 24 h. Interestingly, in the UV61 cells, ROS overexposure by mSMOX delivers an earlier adaptive response to radiation. The enzymatic formation of toxic metabolites has mainly been investigated on wild-type (WT) and multidrug-resistant (MDR) cancer cell lines, using and spermine as substrate of the BSAO enzyme. MDR cells are more sensitive to the toxic polyamine metabolites than WT cells, thus indicating a new therapeutic strategy to overcome MDR tumors. Since SMOX in mammals is differentially activated in a tissue-specific manner and cancer cells can differ in terms of DNA repair and MDR capabilities, it could be of interest to simultaneously treat with very low dose of X-rays and/or to alter SMOX metabolism to generate a differential response in healthy and cancer tissues. IntroductionMammalian cells evolved and constantly live in a highly reactive oxidative environment. In the mammalian organism H 2 O 2 has a central position within the reactive oxygen species (ROS) family. Its formation by several reactions and its controlled inactivation is the basis of redox homeostasis (1,2), since free radicals are highly cytotoxic. Oxidative stress is the result of interactions with macromolecules among highly reactive hydrogen peroxide (H 2 O 2 ) and singlet oxygen ( ). Besides the major interest in identification and advancement of compounds which are either radical scavengers or antioxidants, ROS can alternate between a positive and negative cellular outcomes (3). Insufficient ROS defense mechanisms are mutagenic and promote cell death, apoptosis and autophagy (4). Recently autophagy and apoptosis stimulus by the presence of an H 2 O 2 -induced pathway in human primary and tumor cell lines and in primary cells (5)

show abstract

Section: Msmox Radiation and Ros In A Neuroblastoma Cell Linementioning

confidence: 99%

Section: Msmox and Ros In Aa8 Parental Ber Deficient Em9 And Ner Defmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reactive oxygen species spermine metabolites generated from amine oxidases and radiation represent a therapeutic gain in cancer treatments

Amendola

Cervelli

Fratini

et al. 2013

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…Insights into the role of plant PA catabolism have been constantly gained in the last few years, and it has been correlated with diverse processes such as cell growth and development and programmed cell death (Ha et al, 1997;Yoda et al, 2003;Amendola et al, 2005;RoubelakisAngelakis, 2005a, 2005b;Moschou et al, 2008).…”

mentioning

confidence: 99%

Bridging the Gap between Plant and Mammalian Polyamine Catabolism: A Novel Peroxisomal Polyamine Oxidase Responsible for a Full Back-Conversion Pathway in Arabidopsis

et al. 2008

View full text Add to dashboard Cite

In contrast to animals, where polyamine (PA) catabolism efficiently converts spermine (Spm) to putrescine (Put), plants have been considered to possess a PA catabolic pathway producing 1,3-diaminopropane, D 1 -pyrroline, the corresponding aldehyde, and hydrogen peroxide but unable to back-convert Spm to Put. Arabidopsis (Arabidopsis thaliana) genome contains at least five putative PA oxidase (PAO) members with yet-unknown localization and physiological role(s). AtPAO1 was recently identified as an enzyme similar to the mammalian Spm oxidase, which converts Spm to spermidine (Spd). In this work, we have performed in silico analysis of the five Arabidopsis genes and have identified PAO3 (AtPAO3) as a nontypical PAO, in terms of homology, compared to other known PAOs. We have expressed the gene AtPAO3 and have purified a protein corresponding to it using the inducible heterologous expression system of Escherichia coli. AtPAO3 catalyzed the sequential conversion/ oxidation of Spm to Spd, and of Spd to Put, thus exhibiting functional homology to the mammalian PAOs. The best substrate for this pathway was Spd, whereas the N 1 -acetyl-derivatives of Spm and Spd were oxidized less efficiently. On the other hand, no activity was detected when diamines (agmatine, cadaverine, and Put) were used as substrates. Moreover, although AtPAO3 does not exhibit significant similarity to the other known PAOs, it is efficiently inhibited by guazatine, a potent PAO inhibitor. AtPAO3 contains a peroxisomal targeting motif at the C terminus, and it targets green fluorescence protein to peroxisomes when fused at the N terminus but not at the C terminus. These results reveal that AtPAO3 is a peroxisomal protein and that the C terminus of the protein contains the sorting information. The overall data reinforce the view that plants and mammals possess a similar PA oxidation system, concerning both the subcellular localization and the mode of its action.

show abstract

“…It should also be mentioned in this context that CHX can increase the accumulation of polyamine analogues by deregulating their uptake in CHO cells and favor a rapid induction of apoptosis that was blocked by a PAO inhibitor (Hu and Pegg, 1997). Moreover, ectopical expression of SMO can induce DNA damage and increase the sensitivity to apoptosis of neuroblastoma cells exposed to radiation (Amendola et al, 2005). In our study, enhancement of ROS formation following DENSPM treatment may play a role in the increased susceptibility of chondrocytes to TNF/CHX-induced apoptosis, as indicated by the preventive efficacy of a ROS scavenger (Fig.…”

Section: Discussionmentioning

confidence: 96%

Effect of the polyamine analogue N¹,N¹¹‐diethylnorspermine on cell survival and susceptibility to apoptosis of human chondrocytes

Stanic¹,

Cetrullo²,

Facchini³

et al. 2008

Journal Cellular Physiology

View full text Add to dashboard Cite

Chondrocyte survival is closely linked to cartilage integrity, and forms of chondrocyte apoptotic death can contribute to cartilage degeneration in articular diseases. Since growing evidence also implicates polyamines in the control of cell death, we have been investigating the role of polyamine metabolism in chondrocyte survival and apoptosis. Treatment of human C-28/I2 chondrocytes with N(1),N(11)-diethylnorspermine (DENSPM), a polyamine analogue with clinical relevance as an experimental anticancer agent, inhibited polyamine biosynthesis and induced polyamine catabolism, thus rapidly depleting all main polyamines. DENSPM did not increase significantly caspase activity, but provoked a late cell death associated to DNA fragmentation. A short treatment with DENSPM did not reduce cell viability when given alone, but enhanced caspase-3 and -9 activation in chondrocytes exposed to tumor necrosis factor-alpha (TNF) and cycloheximide (CHX). A longer treatment with DENSPM however reduced caspase response to TNF plus CHX. Depletion of all polyamines obtained by specific inhibitors of polyamine biosynthesis did not cause cell death and contrasted apoptosis by decreasing caspase activities. In conclusion, following DENSPM treatment, C-28/I2 chondrocytes are initially sensitized to caspase 9-dependent apoptosis in the presence of TNF and CHX and may eventually undergo a late and mainly caspase-independent cell death in the absence of other stimuli. Moreover, these results indicate that a reduction of polyamine levels not only leads to inhibition of cell proliferation, but also of caspase-mediated pathways of chondrocyte apoptosis.

show abstract

Direct oxidative DNA damage, apoptosis and radio sensitivity by spermine oxidase activities in mouse neuroblastoma cells

Cited by 24 publications

References 36 publications

Reactive oxygen species spermine metabolites generated from amine oxidases and radiation represent a therapeutic gain in cancer treatments

Reactive oxygen species spermine metabolites generated from amine oxidases and radiation represent a therapeutic gain in cancer treatments

Bridging the Gap between Plant and Mammalian Polyamine Catabolism: A Novel Peroxisomal Polyamine Oxidase Responsible for a Full Back-Conversion Pathway in Arabidopsis

Effect of the polyamine analogue N¹,N¹¹‐diethylnorspermine on cell survival and susceptibility to apoptosis of human chondrocytes

Contact Info

Product

Resources

About

Direct oxidative DNA damage, apoptosis and radio sensitivity by spermine oxidase activities in mouse neuroblastoma cells

Cited by 24 publications

References 36 publications

Reactive oxygen species spermine metabolites generated from amine oxidases and radiation represent a therapeutic gain in cancer treatments

Reactive oxygen species spermine metabolites generated from amine oxidases and radiation represent a therapeutic gain in cancer treatments

Bridging the Gap between Plant and Mammalian Polyamine Catabolism: A Novel Peroxisomal Polyamine Oxidase Responsible for a Full Back-Conversion Pathway in Arabidopsis

Effect of the polyamine analogue N1,N11‐diethylnorspermine on cell survival and susceptibility to apoptosis of human chondrocytes

Contact Info

Product

Resources

About

Effect of the polyamine analogue N¹,N¹¹‐diethylnorspermine on cell survival and susceptibility to apoptosis of human chondrocytes