Publications by authors named "Alfio Distefano"

16 Publications

  • Page 1 of 1

In Vitro Antibacterial, Anti-Adhesive and Anti-Biofilm Activities of (Dombey) Burdet & B.B. Simpson Root Extract against Methicillin-Resistant Strains.

Antibiotics (Basel) 2021 Apr 13;10(4). Epub 2021 Apr 13.

Section of Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, via Santa Sofia 97, 95123 Catania, Italy.

Methicillin-resistant (MRSA) represents a serious threat to public health, due to its large variety of pathogenetic mechanisms. Accordingly, the present study aimed to investigate the anti-MRSA activities of , a medicinal plant native to South America. Through Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass spectrometry, we analyzed the chemical composition of root extract (KLRE). The antibacterial activity of KLRE was determined by the broth microdilution method, also including the minimum biofilm inhibitory concentration and minimum biofilm eradication concentration. Besides, we evaluated the effect on adhesion and invasion of human lung carcinoma A549 cell line by MRSA strains. The obtained results revealed an interesting antimicrobial action of this extract, which efficiently inhibit the growth, biofilm formation, adhesion and invasion of MRSA strains. Furthermore, the chemical analysis revealed the presence in the extract of several flavonoid compounds and type-A and type-B proanthocyanidins, which are known for their anti-adhesive effects. Taken together, our findings showed an interesting antimicrobial activity of KLRE, giving an important contribution to the current knowledge on the biological activities of this plant.
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http://dx.doi.org/10.3390/antibiotics10040428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069196PMC
April 2021

Role of Cigarette Smoke on Angiotensin-Converting Enzyme-2 Protein Membrane Expression in Bronchial Epithelial Cells Using an Air-Liquid Interface Model.

Front Pharmacol 2021 30;12:652102. Epub 2021 Mar 30.

Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.

Prevalence studies of current smoking, among hospitalized COVID-19 patients, demonstrated an unexpectedly low prevalence among patients with COVID-19. The aim of the present study was to evaluate the effect of smoke from cigarettes on ACE-2 in bronchial epithelial cells. Normal bronchial epithelial cells (H292) were exposed to smoke by an air-liquid-interface (ALI) system and ACE-2 membrane protein expression was evaluated after 24 h from exposure. Our transcriptomics data analysis showed a significant selective reduction of membrane ACE-2 expression (about 25%) following smoking exposure. Interestingly, we observed a positive direct correlation between ACE-2 reduction and nicotine delivery. Furthermore, by stratifying GSE52237 as a function of ACE-2 gene expression levels, we highlighted 1,012 genes related to ACE-2 in smokers and 855 in non-smokers. Furthermore, we showed that 161 genes involved in the endocytosis process were highlighted using the online pathway tool KEGG. Finally, 11 genes were in common between the ACE-2 pathway in smokers and the genes regulated during endocytosis, while 12 genes with non-smokers. Interestingly, six in non-smokers and four genes in smokers were closely involved during the viral internalization process. Our data may offer a pharmaceutical role of nicotine as potential treatment option in COVID-19.
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http://dx.doi.org/10.3389/fphar.2021.652102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042260PMC
March 2021

Effects of dutasteride on sex hormones and cerebrospinal steroids in patients treated for benign prostatic hyperplasia.

Endocrine 2021 Mar 9. Epub 2021 Mar 9.

Department of Surgery, Urology Section, University of Catania, 95123, Catania, Italy.

Purpose: Neuroactive steroids may have a role in regulating sexual function. This case-control study assessed whether dutasteride, a 5α-reductase inhibitor used for treatment of patients with benign prostate hyperplasia (BPH), impacts on the levels of neuroactive steroids, leading to erectile dysfunction (ED) and/or hypoactive sexual desire (HSD).

Methods: Forty patients with BPH and moderate-to-severe lower urinary tract symptoms (LUTS), pre-scheduled for prostate transurethral resection or open prostatectomy were enrolled. Twenty of these patients with prostate volume ≤40 mL were treated with α-blockers (Group A) and the remaining 20, with prostate volume >40 mL, with dutasteride plus α-blockers (Group B) for at least 6 months before surgery. Serum sex steroids and gonadotropin levels were measured the day before surgery, and the neuroactive steroid levels were assessed in the cerebrospinal fluid (CSF) collected during spinal anesthesia, at the day of surgery.

Results: Before surgery, the International Index of Erectile Function 5-item score was higher in Group A that Group B (18.8 ± 4.8 vs. 15.1 ± 5.4, p < 0.01). Group A showed lower total testosterone (TT) (4.5 vs.6.4 ng/ml, p < 0.01) and 17β-estradiol (E) (24.3 vs.30.7 pg/ml, p < 0.05) serum levels than Group B. CSF levels of TT (1446.6 vs. 19.9 pg/ml, p < 0.05) and dihydrotestosterone (7.9 vs. 1.4 pg/ml, p < 0.05) were higher and CSF E levels were lower (26.0 vs.36.0 pg/ml, p < 0.01) in Group A than Group B.

Conclusions: A decrease of neuroactive steroids in the CSF of patients treated with dutasteride occurs. This may be one of the mechanisms by which dutasteride may cause ED and HSD.
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http://dx.doi.org/10.1007/s12020-021-02675-4DOI Listing
March 2021

Investigation on the antibacterial activity of electronic cigarette liquids (ECLs): a proof of concept study.

Curr Pharm Biotechnol 2020 Sep 3. Epub 2020 Sep 3.

Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Catania. Italy.

Background: The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms.

Objective: The effect of the combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors.

Methods: Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated.

Results: All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. A higher activity was correlated to the presence of flavors and nicotine.

Discussion: In most cases the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth.

Conclusion: Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.
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http://dx.doi.org/10.2174/1389201021666200903121624DOI Listing
September 2020

Uveal Melanoma Cells Elicit Retinal Pericyte Phenotypical and Biochemical Changes in an in Vitro Model of Coculture.

Int J Mol Sci 2020 Aug 3;21(15). Epub 2020 Aug 3.

Department of Biomedical and Biotechnological Sciences, School of Medicine, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy.

Vascular pericytes are an important cellular component in the tumor microenvironment, however, their role in supporting cancer invasion is poorly understood. We hypothesized that PDGF-BB could be involved in the transition of human retinal pericytes (HRPC) in cancer-activated fibroblasts (CAF), induced by the 92.1 uveal melanoma (UM) cell line. In our model system, HRPC were conditioned by co-culturing with 92.1UM for 6 days (cHRPC), in the presence or absence of imatinib, to block PDGF receptor-β (PDGFRβ). The effects of the treatments were tested by wound healing assay, proliferation assay, RT-PCR, high-content screening, Western blot analysis, and invasion assay. Results showed profound changes in cHRPC shape, with increased proliferation and motility, reduction of NG2 and increase of TGF-β1, α-SMA, vimentin, and FSP-1 protein levels, modulation of PDGF isoform mRNA levels, phospho-PDGFRβ, and PDGFRβ, as well as phospho-STAT3 increases. A reduction of IL-1β and IFNγ and an increase in TNFα, IL10, and TGF-β1, CXCL11, CCL18, and VEGF mRNA in cHRPC were found. Imatinib was effective in preventing all the 92.1UM-induced changes. Moreover, cHRPC elicited a significant increase of 92.1UM cell invasion and active MMP9 protein levels. Our data suggest that retinal microvascular pericytes could promote 92.1UM growth through the acquisition of the CAF phenotype.
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http://dx.doi.org/10.3390/ijms21155557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432414PMC
August 2020

Aerobic Exercise and Metabolic Syndrome: The Role of Sympathetic Activity and the Redox System.

Diabetes Metab Syndr Obes 2020 8;13:2433-2442. Epub 2020 Jul 8.

Department of Clinical and Experimental Medicine, University of Foggia, Foggia 71121, Italy.

Background: Aerobic exercise can greatly assist in reducing collateral effects of metabolic syndrome (MetS). Moreover, aerobic exercise is associated with sympathetic activation and adaptive responses to sustain muscle engagement, changes in the release of Orexin A, a pleiotropic neuropeptide.

Aim: The aim of this study was to analyze the beneficial effects of aerobic exercise without dietary changes, in a cohort of MetS subjects, focusing on the role of sympathetic and orexinergic activity. Several blood parameters linked to MetS ROS production, heart rate, galvanic skin response, d-ROM test, and Orexin A serum levels were evaluated in ten males with MetS (BMI 30-34.9) before and after a period of 6 months of aerobic exercise compared to ten healthy subjects.

Methods: Ten male subjects (aged 54 ± 4.16) with MetS (MetS group) and ten healthy males (aged 49.7 ± 2.79, Healthy group) were told about the study protocol and possible risks, signed the informed consent, and voluntarily participated in the study. Several blood parameters were evaluated in the two tested groups and were re-evaluated in the MetS group after 6 months of training (MetS6M group). The training protocol consisted of more than 30 min/day of walking (average speed of 4.5 km/h) and 3 days/week of aerobic activities (jogging under heart rate control - 120-140 bpm for 45 min).

Results: The results showed that exercise induced a significant increase in GSR and plasma Orexin A but no significant increase in d-ROM values. Significant decreases in the serum ALT enzyme, triglycerides, and total cholesterol were found, while the HDL levels were significantly higher. Finally, a significant reduction of BMI and resting HR were reported.

Conclusion: The results of this study confirm that physical activity is associated with sympathetic activation, having a pivotal role against adverse effects linked to MetS. Moreover, this study demonstrates that, in patients with MetS, Orexin A is involved in hormonal adaptations to exercise.
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http://dx.doi.org/10.2147/DMSO.S257687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354914PMC
July 2020

Hepatitis C virus eradication by direct antiviral agents abates oxidative stress in patients with advanced liver fibrosis.

Liver Int 2020 11 4;40(11):2820-2827. Epub 2020 Aug 4.

Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy.

Background And Aims: HCV eradication improves non-hepatic outcomes such as cardiovascular diseases, although without clearly defined mechanisms. In this study we aimed to assess whether improvement of carotid atherosclerosis may be linked to a reduction in systemic oxidative stress after viral clearance.

Methods: We studied a retrospective cohort of 105 patients (age 62.4 ± 11.2 years; 62 men) with F3/F4 fibrosis, characterized by carotid ultrasonography at baseline and at sustained virologic response (SVR) follow-up. Levels of 8-iso-prostaglandin F (F -isoprostanes) and other oxidative stress markers were measured on frozen sera. Association between change (denoted as Δ) in oxidative stress markers (exposures) and change in carotid intima-media thickness (cIMT) (outcome) was examined using multiple linear regression.

Results: Subclinical atherosclerosis, defined as the presence of carotid plaque and/or cIMT ≥ 0.9, was present in 72% of the cohort. All patients achieved SVR that led to reduction in cIMT (0.92 ± 0.20 vs 0.83 ± 0.21 mm, P < .001). HCV eradication markedly decreased serum levels of F -isoprostanes (620.5 [143.2; 1904.1] vs 119.51 [63.2; 400.6] pg/mL, P < .0001), lipid hydroperoxides (13.8 [6.3; 20.7] vs 4.9 [2.3; 9.6] nmol/μl, P < .0001) and 8-hydroxy-2'-deoxyguanosine (558.9 [321.0; 6301.2] vs 294.51 [215.31; 408.95] pg/mL, P < .0001), whereas increased serum GPx activity (10.44 [4.6; 16.3] vs 13.75 [9.42; 20.63] nmol/min/mL, P = .001). By multiple linear regression analysis ΔcIMT was independently associated with ΔF -isoprostanes (β: 1.746 [0.948; 2.543]; P < .0001) after adjustment for age, baseline F -isoprostanes and baseline IMT.

Conclusions: Besides association of lipid peroxidation with severity of liver disease, the reduction in F -isoprostanes may be involved in the improvement of atherosclerosis after HCV eradication.
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http://dx.doi.org/10.1111/liv.14608DOI Listing
November 2020

Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells.

Aging (Albany NY) 2020 05 12;12(10):9745-9760. Epub 2020 May 12.

Center for Translational Medicine (CTM), International Clinical Research Center (FNUSA-ICRC), St Anne's University Hospital, Brno, Czech Republic.

Uveal melanoma (UM) is the most common primary intraocular tumour in adults. The most accurate prognostic factor of UM is classification by gene expression profiling. Currently, the role of epigenetics is much less defined compared to genetic mechanisms. We recently showed a strong prognostic role of the expression levels of histone variant macroH2A1 in UM patients. Here, we assessed the mechanistic effects of macroH2A1 on UM progression.UM cell lines were stably knocked down (KD) for macroH2A1, and proliferation and colony formation capacity were evaluated. Mitochondrial function was assayed through qPCR and HPLC analyses. Correlation between mitochondrial gene expression and cancer aggressiveness was studied using a bioinformatics approach.MacroH2A1 loss significantly attenuated UM cells proliferation and aggressiveness. Furthermore, genes involved in oxidative phosphorylation displayed a decreased expression in KD cells. Consistently, macroH2A1 loss resulted also in a significant decrease of mitochondrial transcription factor A (TFAM) expression, suggesting impaired mitochondrial replication. Bioinformatics analyses uncovered that the expression of genes involved in mitochondrial metabolism correlates with macroH2A1 and with cancer aggressiveness in UM patients. Altogether, our results suggest that macroH2A1 controls UM cells progression and it may represent a molecular target to develop new pharmacological strategies for UM treatment.
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http://dx.doi.org/10.18632/aging.103241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288915PMC
May 2020

Role of 17-Estradiol on Cell Proliferation and Mitochondrial Fitness in Glioblastoma Cells.

J Oncol 2020 14;2020:2314693. Epub 2020 Feb 14.

Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95125 Catania, Italy.

Gliomas are the most common primary tumors of the central nervous system (CNS) in the adult. Previous data showed that estrogen affects cancer cells, but its effect is cell-type-dependent and controversial. The present study aimed to analyze the effects of estradiol (E2, 5 nM) in human glioblastoma multiforme U87-MG cells and how it may impact on cell proliferation and mitochondrial fitness. We monitored cell proliferation by xCELLigence technology and mitochondrial fitness by assessing the expression of genes involved in mitochondrial biogenesis (PGC1α, SIRT1, and TFAM), oxidative phosphorylation (ND4, Cytb, COX-II, COX IV, NDUFA6, and ATP synthase), and dynamics (OPA1, MNF2, MNF1, and FIS1). Finally, we evaluated Nrf2 nuclear translocation by immunocytochemical analysis. Our results showed that E2 resulted in a significant increase in cell proliferation, with a significant increase in the expression of genes involved in various mechanisms of mitochondrial fitness. Finally, E2 treatment resulted in a significant increase of Nrf2 nuclear translocation with a significant increase in the expression of one of its target genes (i.e., heme oxygenase-1). Our results suggest that E2 promotes proliferation in glioblastoma cells and regulate the expression of genes involved in mitochondrial fitness and chemoresistance pathway.
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http://dx.doi.org/10.1155/2020/2314693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042539PMC
February 2020

Heme Oxygenase-1 and Carbon Monoxide Regulate Growth and Progression in Glioblastoma Cells.

Mol Neurobiol 2020 May 27;57(5):2436-2446. Epub 2020 Feb 27.

Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95125, Catania, Italy.

In human glioma tumours, heme oxygenase-1 (HO-1) is overexpressed when compared with normal brain tissues and during oligodendroglioma progression. However, the molecular mechanisms mediated by HO-1 to promote glioblastoma remain unknown. We therefore aimed at investigating the effect of HO-1 expression and its selective enzymatic inhibition in two different cell lines (i.e. A172 and U87-MG). HO-1 was induced by hemin treatment (10 μM), and VP13/47 (100 μM) was used as a specific non-competitive inhibitor of HO-1 activity. Cell proliferation was measured by cell index measurement (xCelligence technology) and clonogenic assay, whereas cell migration was assessed by wound healing assay. Carbon monoxide-releasing molecules (CORMs) (i.e. CORM-3 and CORM-A1) were also used in a separate set of experiments to confirm the effect of HO-1 by-product in glioblastoma progression further. Our results were further validated using GSE4412 microarray dataset analysis and comparing biopsies overexpressing HO-1 with the rest of the cases. Our results showed that hemin was able to induce both HO-1 gene and protein expression in a cell-dependent manner being A172 more responsive to pharmacological upregulation of HO-1. Hemin, but not CORMs treatment, resulted in a significant increase of cell proliferation following 24 h of treatment as measured by increased cell index and colony formation capacity and such effect was abolished by VP13/47. Interestingly, both hemin and CORMs showed a significant effect on the wound healing assay also exhibiting cell specificity. Finally, our dataset analysis showed a positive correlation of HO-1 gene expression with ITGBI and ITGBII which are membrane receptors involved in cell adhesion, embryogenesis, tissue repair, immune response and metastatic diffusion of tumour cells. In conclusion, our data suggest that HO-1 and its by-product CO exhibit a cell-specific effect on various aspects of disease progression and are associated with a complex series of molecular mechanisms driving cell proliferation, survival and metastasis.
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http://dx.doi.org/10.1007/s12035-020-01869-7DOI Listing
May 2020

Ethanol-Mediated Stress Promotes Autophagic Survival and Aggressiveness of Colon Cancer Cells via Activation of Nrf2/HO-1 Pathway.

Cancers (Basel) 2019 Apr 10;11(4). Epub 2019 Apr 10.

Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), Institute of Biochemistry, University of Palermo, 90127 Palermo, Italy.

Epidemiological studies suggest that chronic alcohol consumption is a lifestyle risk factor strongly associated with colorectal cancer development and progression. The aim of the present study was to examine the effect of ethanol (EtOH) on survival and progression of three different colon cancer cell lines (HCT116, HT29, and Caco-2). Our data showed that EtOH induces oxidative and endoplasmic reticulum (ER) stress, as demonstrated by reactive oxygen species (ROS) and ER stress markers Grp78, ATF6, PERK and, CHOP increase. Moreover, EtOH triggers an autophagic response which is accompanied by the upregulation of beclin, LC3-II, ATG7, and p62 proteins. The addition of the antioxidant N-acetylcysteine significantly prevents autophagy, suggesting that autophagy is triggered by oxidative stress as a prosurvival response. EtOH treatment also upregulates the antioxidant enzymes SOD, catalase, and heme oxygenase (HO-1) and promotes the nuclear translocation of both Nrf2 and HO-1. Interestingly, EtOH also upregulates the levels of matrix metalloproteases (MMP2 and MMP9) and VEGF. Nrf2 silencing or preventing HO-1 nuclear translocation by the protease inhibitor E64d abrogates the EtOH-induced increase in the antioxidant enzyme levels as well as the migration markers. Taken together, our results suggest that EtOH mediates both the activation of Nrf2 and HO-1 to sustain colon cancer cell survival, thus leading to the acquisition of a more aggressive phenotype.
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http://dx.doi.org/10.3390/cancers11040505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521343PMC
April 2019

The Biochemical and Pharmacological Properties of Ozone: The Smell of Protection in Acute and Chronic Diseases.

Int J Mol Sci 2019 Feb 1;20(3). Epub 2019 Feb 1.

Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95125 Catania, Italy.

Ozone therapy has been widely used in everyday clinical practice over the last few years, leading to significant clinical results in the treatment of herniated discs and pain management. Nevertheless, further studies have demonstrated its potential efficacy and safety under other clinical and experimental conditions. However, some of these studies showed controversial results regarding the safety and efficacy of ozone therapy, thus mining its potential use in an everyday clinical practice. To this regard, it should be considered that extensive literature review reported the use of ozone in a significant different dose range and with different delivery systems. The aim of the present review is to describe the various pharmacological effects of ozone in different organs and clinical conditions and to provide possible biochemical and molecular insights for ozone biological properties, thus providing a possible explanation for various controversial clinical outcomes described in the scientific literature.
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http://dx.doi.org/10.3390/ijms20030634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387239PMC
February 2019

Consequences on aging process and human wellness of generation of nitrogen and oxygen species during strenuous exercise.

Aging Male 2020 Mar 27;23(1):14-22. Epub 2018 Jun 27.

Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Impairment of antioxidant defense system and increase in metabolic rate and production of reactive oxygen species have been demonstrated in strenuous exercise. Both at rest and during contractile activity, skeletal muscle generates a very complex set of reactive nitrogen and oxygen species; the main generated are superoxide and nitric oxide. The nature of the contractile activity influences the pattern and the magnitude of this reactive oxygen and nitrogen species (ROS) generation. The intracellular pro-oxidant/antioxidant homeostasis undergoes alteration owing to strenuous exercise and the major identified sources of intracellular free radical generation during physical activity are the mitochondrial electron transport chain, polymorphoneutrophil, and xanthine oxidase. Reactive oxygen species increased tissue susceptibility to oxidative damage and pose a serious threat to the cellular antioxidant defense system. The possible dangerous consequences of the aging process and human wellness are emphasized in this review.
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http://dx.doi.org/10.1080/13685538.2018.1482866DOI Listing
March 2020

Heme Oxygenase Inhibition Sensitizes Neuroblastoma Cells to Carfilzomib.

Mol Neurobiol 2019 Feb 10;56(2):1451-1460. Epub 2018 Jun 10.

Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia, 97, 95125, Catania, Italy.

Neuroblastoma (NB) is an embryonic malignancy affecting the physiological development of adrenal medulla and paravertebral sympathetic ganglia in early infancy. Proteasome inhibitors (PIs) (i.e., carfilzomib (CFZ)) may represent a possible pharmacological treatment for solid tumors including NB. In the present study, we tested the effect of a novel non-competitive inhibitor of heme oxygenase-1 (HO-1), LS1/71, as a possible adjuvant therapy for the efficacy of CFZ in neuroblastoma cells. Our results showed that CFZ increased both HO-1 gene expression (about 18-fold) and HO activity (about 8-fold), following activation of the ER stress pathway. The involvement of HO-1 in CFZ-mediated cytotoxicity was further confirmed by the protective effect of pharmacological induction of HO-1, significantly attenuating cytotoxicity. In addition, HO-1 selective inhibition by a specific siRNA increased the cytotoxic effect following CFZ treatment in NB whereas SnMP, a competitive pharmacological inhibitor of HO, showed no changes in cytotoxicity. Our data suggest that treatment with CFZ produces ER stress in NB without activation of CHOP-mediated apoptosis, whereas co-treatment with CFZ and LS1/71 led to apoptosis activation and CHOP expression induction. In conclusion, our study showed that treatment with the non-competitive inhibitor of HO-1, LS1 / 71, increased cytotoxicity mediated by CFZ, triggering apoptosis following ER stress activation. These results suggest that PIs may represent a possible pharmacological treatment for solid tumors and that HO-1 inhibition may represent a possible strategy to overcome chemoresistance and increase the efficacy of chemotherapic regimens.
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http://dx.doi.org/10.1007/s12035-018-1133-6DOI Listing
February 2019

Antimicrobial and Anti-Proliferative Effects of Skin Mucus Derived from Dasyatis pastinaca (Linnaeus, 1758).

Mar Drugs 2017 Nov 1;15(11). Epub 2017 Nov 1.

Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95124, Italy.

Resistance to chemotherapy occurs in various diseases (i.e., cancer and infection), and for this reason, both are very difficult to treat. Therefore, novel antimicrobial and chemotherapic drugs are needed for effective antibiotic therapy. The aim of the present study was to assess the antimicrobial and anti-proliferative effects of skin mucus derived from (Linnaeus, 1758). Our results showed that skin mucus exhibited a significant and specific antibacterial activity against Gram-negative bacteria but not against Gram-positive bacteria. Furthermore, we also observed a significant antifungal activity against some strains of spp. Concerning anti-proliferative activity, we showed that fish mucus was specifically toxic for acute leukemia cells (HL60) with an inhibition of proliferation in a dose dependent manner (about 52% at 1000 μg/mL of fish skin mucous, FSM). Moreover, we did not observe effects in healthy cells, in neuroblastoma cells (SH-SY5Y), and multiple myeloma cell lines (MM1, U266). Finally, it exhibited strong expression and activity of chitinase which may be responsible, at least in part, for the aforementioned results.
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http://dx.doi.org/10.3390/md15110342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706032PMC
November 2017

Metformin: A Bridge between Diabetes and Prostate Cancer.

Front Oncol 2017 11;7:243. Epub 2017 Oct 11.

Department of Drug Science, Biochemistry Section, University of Catania, Catania, Italy.

Prostate cancer (PCa) has become the most frequent type of cancer in men. Recent data suggest that diabetic patients taking metformin have a lower incidence of certain cancer, including PCa. Metformin is the most common drug used in type II diabetes mellitus; its use has been shown to lower the incidence of several cancers, although there are ambiguous data about the anticancer activity of metformin. A large number of studies examined the potential antineoplastic mechanism of metformin although it is not still completely understood. This review summarizes the literature concerning the effects of metformin on PCa cells, highlighting its numerous mechanisms of action through which it can act. We analyze the possible causes of the discordances regarding the impact of metformin on risk of PCa; we discuss the latest findings in this field, suggesting that metformin may have a future role in the management of PCa both as monotherapy and in combination with other drugs.
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http://dx.doi.org/10.3389/fonc.2017.00243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641539PMC
October 2017