Neuroprotective, antioxidant and antiproliferative activity of grapefruit IntegroPectin on SH-SY5Y cells

Tested in vitro on SH-SY5Y neuroblastoma cells, grapefruit IntegroPectin is a powerful neuro-protective, antioxidant and antiproliferative agent. The strong antioxidant properties of grape-fruit IntegroPectin, and its ability to preserve mitochondrial membrane potential and mor-phology, severely impaired in neurodegenerative disorders, make this new biopolymer highly soluble in water an attractive therapeutic agent for oxidative stress-associated brain disorders. Similarly, the ability of this new citrus pectin rich in naringin, linalool, linalool oxide and lim-onene adsorbed at the outer surface to inhibit cell proliferation or even kill, at high doses, neo-plastic cells, coupled to its excellent health and safety profile, opens up new therapeutic strate-gies in cancer research. In order to take full advantage of its vast therapeutic and preventive po-tential, detailed studies of molecular mechanism involved in the antiproliferative and neuro-protective of IntegroPectin are urgently needed.

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Protective, Antioxidant and Antiproliferative Activity of Grapefruit IntegroPectin on SH-SY5Y Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22179368 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9368

Author(s):

Domenico Nuzzo ◽

Miriana Scordino ◽

Antonino Scurria ◽

Costanza Giardina ◽

Francesco Giordano ◽

...

Keyword(s):

Antioxidant Properties ◽

Neuroblastoma Cells ◽

Therapeutic Strategies ◽

Brain Disorders ◽

Citrus Pectin ◽

Linalool Oxide ◽

Antiproliferative Agent ◽

High Doses ◽

Inhibit Cell Proliferation

Tested in vitro on SH-SY5Y neuroblastoma cells, grapefruit IntegroPectin is a powerful protective, antioxidant and antiproliferative agent. The strong antioxidant properties of this new citrus pectin, and its ability to preserve mitochondrial membrane potential and morphology, severely impaired in neurodegenerative disorders, make it an attractive therapeutic and preventive agent for the treatment of oxidative stress-associated brain disorders. Similarly, the ability of this pectic polymer rich in RG-I regions, as well as in naringin, linalool, linalool oxide and limonene adsorbed at the outer surface, to inhibit cell proliferation or even kill, at high doses, neoplastic cells may have opened up new therapeutic strategies in cancer research. In order to take full advantage of its vast therapeutic and preventive potential, detailed studies of the molecular mechanism involved in the antiproliferative and neuroprotective of this IntegroPectin are urgently needed.

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Anticancer and Antioxidant Properties of Terpinolene in Rat Brain Cells

Archives of Industrial Hygiene and Toxicology ◽

10.2478/10004-1254-64-2013-2365 ◽

2013 ◽

Vol 64 (3) ◽

pp. 415-424 ◽

Cited By ~ 24

Author(s):

Elanur Aydin ◽

Hasan Türkez ◽

Şener Taşdemir

Keyword(s):

Biological Activities ◽

Antioxidant Properties ◽

Neuroblastoma Cells ◽

In Vitro Study ◽

Cell Types ◽

Damage Potential ◽

Total Antioxidant ◽

Antiproliferative Agent ◽

Total Oxidative Stress

Abstract Terpinolene (TPO) is a natural monoterpene present in essential oils of many aromatic plant species. Although various biological activities of TPO have been demonstrated, its neurotoxicity has never been explored. In this in vitro study we investigated TPO’s antiproliferative and/or cytotoxic properties using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test, genotoxic damage potential using the single-cell gel electrophoresis (SCGE), and oxidative effects through total antioxidant capacity (TAC) and total oxidative stress (TOS) in cultured primary rat neurons and N2a neuroblastoma cells. Dose-dependent effects of TPO (at 10 mg L-1, 25 mg L-1, 50 mg L-1, 100 mg L-1, 200 mg L-1, and 400 mg L-1) were tested in both cell types. Significant (P<0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the dose of 100 mg L-1 and in N2a neuroblastoma cells starting with 50 mg L-1. TPO was not genotoxic in either cell type. In addition, TPO treatment at 10 mg L-1, 25 mg L-1, and 50 mg L-1 increased TAC in primary rat neurons, but not in N2a cells. However, at concentrations above 50 mg L-1 it increased TOS in both cell types. Our findings clearly demonstrate that TPO is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.

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In-vitro- und In-vivo-Wirkung von Schilddrüsenhormon auf das Wachstum von Neuroblastomzellen

Nuklearmedizin ◽

10.1055/s-0038-1629520 ◽

1990 ◽

Vol 29 (03) ◽

pp. 120-124

Author(s):

R. P. Baum ◽

E. Rohrbach ◽

G. Hör ◽

B. Kornhuber ◽

E. Busse

Keyword(s):

Cell Differentiation ◽

Neuroblastoma Cells ◽

Control Group ◽

Initial Value ◽

Initial Rise ◽

Biphasic Effect ◽

Contrast Microscopy ◽

Morphological Sign

The effect of triiodothyronine (T3) on the differentiation of cultured neuroblastoma (NB) cells was studied after 9 days of treatment with a dose of 10-4 M/106 cells per day. Using phase contrast microscopy, 30-50% of NB cells showed formation of neurites as a morphological sign of cellular differentiation. The initial rise of the mitosis rate was followed by a plateau. Changes in cyclic nucleotide content, in the triphosphates and in the activity of the enzyme ornithine decarboxylase (ODC) were assessed in 2 human and 2 murine cell lines to serve as biochemical parameters of the cell differentiation induced by T3. Whereas the cAMP level increased significantly (3 to 7 fold compared with its initial value), the cGMP value dropped to 30 to 50% of that of the control group. ATP and GTP increased about 200%, the ODC showed a decrease of about 50%. The present studies show a biphasic effect of T3 on neuroblastoma cells: the initial rise of mitotic activity is followed by increased cell differentiation starting from day 4 of the treatment.

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In Vivo Effect of Suloctidil as an Antiplatelet Agent

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646799 ◽

1979 ◽

Vol 41 (03) ◽

pp. 465-474 ◽

Cited By ~ 7

Author(s):

Marcia R Stelzer ◽

Thomas S Burns ◽

Robert N Saunders

Keyword(s):

Ex Vivo ◽

Antiplatelet Agent ◽

Ratio Method ◽

Platelet Aggregate ◽

Permanent Effect ◽

Platelet Aggregates ◽

5 Ht Uptake ◽

High Doses

SummaryThe relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5- HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.

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Daunorubicin and Platelet Function

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650125 ◽

1981 ◽

Vol 45 (01) ◽

pp. 038-042 ◽

Cited By ~ 9

Author(s):

M E Pogliani ◽

R Fantasia ◽

G Lambertenghi-Deliliers ◽

E Cofrancesco

Keyword(s):

Electron Microscope ◽

Cellular Membrane ◽

Hemorrhagic Diathesis ◽

Clot Retraction ◽

Freezing And Thawing ◽

Platelet Factor ◽

High Doses ◽

Very High ◽

Platelet Functions

SummaryThe influence of Daunorubicin on some platelet functions in vitro was investigated, using different concentrations of the drug (0.01-0.02-0.04 μg/ml). Daunorubicin was shown to inhibit Collagen and Thrombin induced platelet aggregation and the intensity of inhibition depended on both drug concentration and the time of preincubation.Daunorubicin was also shown to inhibit the release reaction, the platelet prostaglandin pathway and the availability platelet factor 3; the drug at concentrations for clinical use does not damage the platelet membrane, as is the case with the freezing and thawing test, in platelet uptake of 14C-serotonin and as confirmed by the electron microscope. When very high doses (0.16 mg) of Daunorubicin are used, lysis of the platelets can be observed and this is confirmed under the electron microscope by the presence of empty platelets with fractures at the level of the cytoplasmic membrane.Finally, Daunorubicin causes irreversible inhibition of reptilase clot-retraction, even if this is less severe than with Vincristine. Working with gel-filtered platelets, it would appear that the inhibition exercised by the drug on platelet reactions is not caused through modifications in Ca++ metabolism.The authors suggest that Daunorubicin, at the dosages used clinically, induces in vitro thrombocytopathy without damaging the cellular membrane as confirmed by the electron microscope.This impairment of platelet functions could play a part in hemorrhagic diathesis observed during Daunorubicin therapy.

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Effects of Two Different Doses of Hirudin on APTT, Determined with Eight Different Reagents

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653754 ◽

1995 ◽

Vol 73 (02) ◽

pp. 219-222 ◽

Cited By ~ 4

Author(s):

Manuel Monreal ◽

Luis Monreal ◽

Rafael Ruiz de Gopegui ◽

Yvonne Espada ◽

Ana Maria Angles ◽

...

Keyword(s):

Ex Vivo ◽

Anticoagulant Activity ◽

Subcutaneous Administration ◽

In Vitro Study ◽

Ex Vivo Model ◽

Suitable Candidate ◽

Significant Prolongation ◽

High Doses ◽

Different Doses

SummaryThe APTT has been considered the most suitable candidate to monitor the anticoagulant activity of hirudin. However, its use is hampered by problems of standardization, which make the results heavily dependent on the responsiveness of the reagent used. Our aim was to investigate if this different responsiveness of different reagents when added in vitro is to be confirmed in an ex vivo study.Two different doses of r-hirudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered subcutaneously to 20 New Zealand male rabbits, and the differences in prolongation of APTT 2 and 12 h later were compared, using 8 widely used commercial reagents. All groups exhibited a significant prolongation of APTT 2 h after sc administration of hirudin, both at low and high doses. But this prolongation persisted 12 h later only when the PTTa reagent (Boehringer Mannheim) was used. In general, hirudin prolonged the APTT most with the silica- based reagents.In a further study, we compared the same APTT reagents in an in vitro study in which normal pooled plasma was mixed with increasing amount of hirudin. We failed to confirm a higher sensitivity for silica- containing reagents. Thus, we conclude that subcutaneous administration of hirudin prolongs the APTT most with the silica-based reagents, but this effect is exclusive for the ex vivo model.

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QUALITATIVE AND QUANTITATIVE PHYTOCHEMICAL SCREENING AND IN VITRO ANTIOXIDANT EVALUATION OF PERGULARIA DAEMIA

FLORA AND FAUNA ◽

10.33451/florafauna.v24i2pp350-354 ◽

2018 ◽

Vol 24 (2) ◽

Author(s):

GITA MISHRA ◽

HEMESHWER KUMAR CHANDRA ◽

NISHA SAHU ◽

SATENDRA KUMAR NIRALA ◽

MONIKA BHADAURIA

Keyword(s):

Reducing Sugars ◽

Antioxidant Properties ◽

Phytochemical Analysis ◽

Phytochemical Screening ◽

Qualitative And Quantitative ◽

The Family ◽

Ethanolic Extracts ◽

Antioxidant Evaluation ◽

In Vitro Antioxidant Activity

Pergularia daemia belongs to the family Asclepiadaceae, known to have anticancer, anti-inflammatory activity. Aim of the present study was to evaluate qualitative and quantitative phytochemical and antioxidant properties of ethanolic extracts of leaf, stem and root parts of P. daemia . Preliminary phytochemical analysis and in vitro antioxidant properties were evaluated by standard methods. The qualitative phytochemical analysis of P. daemia showed presence of flavonoids, tannins, alkaloid, phytosterol, carbohydrate, phenol, saponin, glycosides, terpenoids, steroids proteins and reducing sugars. Quantitative analysis showed polyphenol, flavonoid, flavonone, flavone and flavonol in P. daemia leaves, stem and root in considerable quantity. The in vitro antioxidant activity of P. daemia clearly demonstrated that leaf, stem and root parts have prominent antioxidant properties and was effective in scavenging free radicals.

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Molecular iodine synergized and sensitized neuroblastoma cells to the antineoplastic effect of ATRA

Endocrine Related Cancer ◽

10.1530/erc-20-0354 ◽

2020 ◽

Vol 27 (12) ◽

pp. 699-710

Author(s):

Irasema Mendieta ◽

Gabriel Rodríguez-Gómez ◽

Bertha Rueda-Zarazúa ◽

Julia Rodríguez-Castelán ◽

Winniberg Álvarez-León ◽

...

Keyword(s):

Residual Disease ◽

Neuroblastoma Cells ◽

Survivin Expression ◽

Body Weight Loss ◽

Immunohistochemical Analysis ◽

Molecular Iodine ◽

Tyrosine Kinase Receptor ◽

Adjuvant Effect

Neuroblastoma (NB) is the most common solid childhood tumor, and all-trans retinoic acid (ATRA) is used as a treatment to decrease minimal residual disease. Molecular iodine (I2) induces differentiation and/or apoptosis in several neoplastic cells through activation of PPARγ nuclear receptors. Here, we analyzed whether the coadministration of I2 and ATRA increases the efficacy of NB treatment. ATRA-sensitive (SH-SY5Y), partially-sensitive (SK-N-BE(2)), and non-sensitive (SK-N-AS) NB cells were used to analyze the effect of I2 and ATRA in vitro and in xenografts (Foxn1 nu/nu mice), exploring actions on cellular viability, differentiation, and molecular responses. In the SH-SY5Y cells, 200 μM I2 caused a 100-fold (0.01 µM) reduction in the antiproliferative dose of ATRA and promoted neurite extension and neural marker expression (tyrosine hydroxylase (TH) and tyrosine kinase receptor alpha (Trk-A)). In SK-N-AS, the I2 supplement sensitized these cells to 0.1 μM ATRA, increasing the ATRA-receptor (RARα) and PPARγ expression, and decreasing the Survivin expression. The I2 supplement increased the mitochondrial membrane potential in SK-N-AS suggesting the participation of mitochondrial-mediated mechanisms involved in the sensibilization to ATRA. In vivo, oral I2 supplementation (0.025%) synergized the antitumor effect of ATRA (1.5 mg/kg BW) and prevented side effects (body weight loss and diarrhea episodes). The immunohistochemical analysis showed that I2 supplementation decreased the intratumoral vasculature (CD34). We suggest that the I2 + ATRA combination should be studied in preclinical and clinical trials to evaluate its potential adjuvant effect in addition to conventional treatments.

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