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Abstract This study assessed the impact of fermented cow and soy milk supplemented with curcumin on enhancement the health status of female Swiss mice under Ehrlich ascites carcinoma (EAC) condition. Both types of milk were fermented by Lactobacillus plantarum EMCC 1027. Ninety-five grams of basal diet mixed with five grams of either fermented cow or soy milk supplemented with curcumin. Induction of Ehrlich tumor-bearing mice synergized by intraperitoneal injection with 1 × 106 Ehrlich ascites tumor cells after one week of the adaptation period. Our results showed that levels of survival rate were increased to 117% in mice that were fed fermented cow and soy milk while supplementation of fermented soy milk with curcumin improved the survival rate to 150%. The concentration of glutathione and superoxide dismutase in Ehrlich tumor-bearing was increased after feeding with both types of fermented milk. Fermented soy milk supplemented with curcumin showed the highest reduction levels of plasma tumor necrosis factor (TNF)-α and interleukin-6. The relative gene expression TNF-α was also significantly (P

This study assessed the impact of fermented cow and soy milk supplemented with curcumin on enhancement the health status of female Swiss mice under Ehrlich ascites carcinoma (EAC) condition. Both types of milk were fermented by Lactobacillus plantarum EMCC 1027. Ninety-five grams of basal diet mixed with five grams of either fermented cow or soy milk supplemented with curcumin. Induction of Ehrlich tumor-bearing mice synergized by intraperitoneal injection with 1 × 106 Ehrlich ascites tumor cells after one week of the adaptation period. Our results showed that levels of survival rate were increased to 117% in mice that were fed fermented cow and soy milk while supplementation of fermented soy milk with curcumin improved the survival rate to 150%. The concentration of glutathione and superoxide dismutase in Ehrlich tumor-bearing was increased after feeding with both types of fermented milk. Fermented soy milk supplemented with curcumin showed the highest reduction levels of plasma tumor necrosis factor (TNF)-α and interleukin-6. The relative gene expression TNF-α was also significantly (P < 0.05) down-regulated in mice that were fed fermented soy milk with curcumin. The viable count of lactobacilli and bifidobacteria in feces samples was increased when mice fed both types of fermented milk. Dietary feeding with fermented cow or soy milk supplemented with curcumin has an ameliorative impact on the survival rate, antioxidant capacity, inflammation, fecal microbiota in EAC mouse model. Further research is still needed to investigate the molecular mechanisms in this tumor.Article Highlights: Fermented cow or soy milk- curcumin formula enhances the survival rate of EAC mice. It enhances antioxidant capacity and lowers pro-inflammatory cytokines. It increases fecal lactobacilli and bifidobacteria. [ABSTRACT FROM AUTHOR]

We investigated the potential influence of kefir-induced juglone and resveratrol fractions (JRK) against Ehrlich Ascites Carcinoma (EAC) bearing BALB/c male mice. Kefir yeast was grown in the cell culture supplemented with juglone and resveratrol (1:2). After 48 h incubation, JRK solution was applied (0.1 mL/day i.p.) to the EAC-bearing mice throughout five days. Molecular regulatory mechanisms of apoptotic and anti-apoptotic pathway components were evaluated in the plasma of mice and isolated EAC cells with ELISA, qRT-PCR, and immunocytchemical experiments. EAC-induced upregulation in Bcl-2 and downregulation in Caspase-3 were normalized with JRK in the plasma of mice. Additionally, JRK upregulated the expression levels of apoptotic Bax, p53, Caspase-3,8,9, and APAF-1 proteins together with BAX, CASPASE-8, and CASPASE-9 genes in isolated EAC cells. These changes were also associated with decreased expression levels of anti-apoptotic Bcl-2 and Bcl-xl proteins. Immunocytochemical studies also confirmed the activation of apoptotic pathways and repression of anti-apoptotic proteins in EAC cells with JRK treatment. JRK activates apoptotic pathway and inhibits anti-apoptotic genes and proteins in Ehrlich ascites carcinoma- bearing BALB/c mice that could be beneficial in cancer treatment. [ABSTRACT FROM AUTHOR]

Graphene oxide (GO) nanosheet is a drug delivery system due to its structural properties, which can be augmented in presence of folic acid (FA). This study aimed to compare the efficacy of GO as a passive (GO/DOX) and active (GO/FA/DOX) forms for delivering doxorubicin (DOX). These two forms of conjugates were characterized before and after loading of DOX to confirm the conjugation as well as their properties including size and thermal stability. Using Ehrlich ascites carcinoma (EAC) cell line, the antitumor effect was evaluated by MTT assay in vitro and cell count; tumor cell cycle and apoptosis were evaluated by flow cytometry in vivo. The results showed that the loading percentages of DOX onto GO (GO/DOX) and GO/FA/DOX were 91% and 83%, respectively. TEM, FT-IR, and TGA confirmed the nano size, physical conjugation by shifted groups, and thermal stability. In vitro, the conjugates induced similar decrease of EAC cell viability, but still lower than those of free DOX. Treatment of EAC-bearing mice with GO/DOX or GO/FA/DOX forms induced significant decreases of the total numbers of EAC cells by 79% and 97%, respectively, as compared with free DOX (97%). DOX, GO/DOX, and GO/FA/DOX induced cell cycle arrest at G0, G1, and S phase, respectively. These conjugates also induced significant apoptosis with different profiles on viable, early, and late apoptotic EAC cells. In conclusion, loading DOX on GO nanosheet activated with FA can induce antitumor effect similar to those of free DOX but with different mechanisms. [ABSTRACT FROM AUTHOR]

Summary: Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects. [ABSTRACT FROM AUTHOR]

Schistosomiasis is the third most devastating tropical disease worldwide caused by blood flukes of the genus Schistosoma. Praziquantel (PZQ) is the drug of choice for treating all species of schistosomes. However, PZQ kills only adult Schistosoma worms, not immature stages. The inability of PZQ to abort early infection or prevent re-infection, and the lack of prophylactic effect prompt the need for novel drugs and strategies for the prevention of schistosomiasis. Tumor burden can be developed in Schistosoma-infected patients. The present study aimed to determine the host responses to mutual interaction between cancer, represented by Ehrlich ascites, and infection, represented by Schistosomiasis. Mice infected with Schistosoma and challenged with tumor 4-5 weeks later showed the same anti-schistosomal (worm and egg burden) and antitumor (total tumor cell count and mouse survival) parameters when compared to mice infected with Schistosoma alone or challenged with tumor cells alone. As expected, combinatorial treatment with PZQ and cisplatin of Schistosoma-infected mice that were challenged with tumor cell line decreased the tumor burden as well as the worm and egg burden after treatment as compared to the non-treated controls; while the worm burden and egg counts were significantly decreased (P <0.001) in treated group (VI) treated with cisplatin (0.5 mg/kg), group (VII) treated with cisplatin (2 mg/kg), group (VIII) treated with PZQ/cisplatin (0.5 mg/kg) and group (IX) treated with PZQ / cisplatin (2 mg/kg) by 44.55%, 74%, 100% and 97.8% in worm burden, and by 47%, 78.7%, 96% and 97% in liver egg count, respectively than that of group (II) non treated S. mansoni infected alone and (IV) non treated S. mansoni/EAC alone. Also, Group IX caused a significant reduction (P <0.05) in worm burden than that of group VI. Also, total ascetic volume and the tumor cell counts in Ehrlich's ascites carcinoma (EAC)-cells were significantly decreased (P <0.001) in groups VIII and IX than that of the group (III) non-treated (EAC) inoculated alone. There was no mutual interaction between schistosomiasis infection and tumor burden. Also, whereas, PZQ did not affect on the antitumor parameters, cisplatin even at low doses had anti-schistosomal effects. [ABSTRACT FROM AUTHOR]

Abstract Cr(III), Mn(II), Fe(III), Cd(II), Zn(II) and Hg(II) complexes derived from carbohydrazone ligand were synthesized and characterized by spectroscopic methods, DFT calculations and TGA analysis. IR spectra together with DFT optimization revealed that the ligand uses its two (C N) azomthine in coordination with either Mn(II), Fe(III) or Zn(II) ions. While, Cd(II) and Hg(II) ions coordinates via the nitrogen atoms of the two pyridyl groups. On the other hand, the coordination takes place through the two (C N) azomthine and the (C O) carbonyl groups in Cr(III) complex. On the basis of the electronic spectra and as the magnetic measurements, an octahedral coordination geometry was proposed in case of Cr(III) and Fe(III) complexes and a tetrahedral geometry in case of Mn(II) complex. Kinetic and thermodynamic parameters of the isolated complexes were estimated using Coats-Redfern and Horowitz-Metzger models. The antioxidant (DDPH and ABTS methods), anti-hemolytic and cytotoxic activities of the compounds have been screened. The DDPH and ABTS antioxidant activity was investigated and indicated that Zn(II) complex exhibited the highest antioxidant activity. While, Fe(III) complex had significantly the same percentage of hemolysis as that of the positive control. With respect to antitumor activity, H 2 APEC and Zn(II) complex demonstrated the potent activity followed by Fe(III) complex. Graphical abstract Image 1 Highlights • Cr(III), Mn(II), Fe(III), Cd(II), Zn(II) and Hg(II) complexes of biscarbohydrazone. • Elemental analysis, spectral characterization of the ligands and their complexes. • Thermal behavior were studied for the metal complexes using TGA technique. • DFT studies. • Erythrocyte hemolysis, antioxidant activity and cytotoxicity were tested. [ABSTRACT FROM AUTHOR]

Plants from the genus Alternanthera are thought to possess antimicrobial and antiviral properties. In Brazilian folk medicine, the aqueous extract of A. tenella Colla is used for its anti-inflammatory activity. The present study investigated the immunomodulatory property of A. tenella extract by evaluating the antibody production in male albino Swiss mice weighing 20-25 g (10 per group). The animals received standard laboratory diet and water ad libitum. The effect of A. tenella extract (5 and 50 mg/kg, ip) was evaluated in mice immunized with sheep red blood cells (SRBC 10%, ip) as T-dependent antigen, or in mice stimulated with mitogens (10 µg, Escherichia coli lipopolysaccharide, LPS, ip). The same doses (5 and 50 mg/kg, ip) of A. tenella extract were also tested for antitumor activity, using the Ehrlich ascites carcinoma as model. The results showed that 50 mg/kg A. tenella extract ip significantly enhanced IgM (64%) and IgG2a (50%) antibody production in mice treated with LPS mitogen. The same dose had no effect on IgM-specific response, whereas the 5 mg/kg treatment caused a statiscally significant reduction of anti-SRBC IgM-specific antibodies (82%). The aqueous extract of A. tenella (50 mg/kg) increased the life span (from 16 ± 1 to 25 ± 1 days) and decreased the number of viable tumor cells (59%) in mice with Ehrlich ascites carcinoma. The present findings are significant for the development of alternative, inexpensive and perhaps even safer strategies for cancer treatment.

Highlights: [•] Preparation of Cr3+, Mn2+ and Fe3+ complexes of carbohydrazones. [•] Elemental analysis, spectral characterization of the ligands and their complexes. [•] Thermal behavior of the solid metal complexes was studied using TGA technique. [•] DFT studies. [•] The compounds were screened for erythrocyte hemolysis, antioxidant activity and cytotoxicity. [Copyright &y& Elsevier]

Research for natural compounds with beneficial biological activities or antineoplastic capacity is an important target in drug discovery. An example of this type of bioactive compound is epigallocatechin 3-gallate (EGCG), which is the major polyphenol in green tea. The treatment with 10 µM EGCG of Ehrlich ascites carcinoma cells collected from the ascitic fluid of BALB/c mice harbouring 8--10 days old ascitic tumor determined a reduction of cell viability versus control. The value for cell viability expressed as % of control being 86.6% at 24h, 62.6% at 48h, 72.3% at 72h, and 81% at 92h. The cell growth data sustains cell viability data; EGCG did not induce necrosis but was able to induce apoptosis in investigated Ehrlich ascites carcinoma cells. There were no significant differences observed in IL-6 and TNF-α production to any group throughout the study at 24h, meanwhile at 48h a decreased level for both cytokines evaluated was observed. However, IL-6 and TNF-α was slightly reduced in protein expression at 48h. Experimental data exhibits significant antitumor activity of EGCG, being time dependent, but still remains to be validated on in vitro models. [ABSTRACT FROM AUTHOR]

The aim of this study is to develop ascorbyl palmitate (ASP) loaded doxorubicin (DOX) pegylated liposomes and to evaluate their targeting potential to tumor. We have prepared conventional (DL), pegylated DOX liposomes with (SDL) and without ascorbyl palmitate (SDL-A). The vesicle size in all the formulations was within the range 105--120 nm and in  vitro release studies in serum confirmed the stability of the liposomes. Biodistribution studies carried out in Ehrlich ascites tumor bearing mice indicate higher area under the curve for SDL and SDL-A liposomes compared to DL and plain drug solution. Drug targeting index assessed from tumor-to-serum concentration ratio and therapeutic availability of DOX in tumor tissue was also significantly higher for pegylated liposomes. In conclusion, biodistribution study reveals that the presence of ascorbyl palmitate alters the distribution pattern of liposomes and paves way for better drug targeting. [ABSTRACT FROM AUTHOR]

In the present work, we have studied the effects of two titanocenes, biscyclopentadienyldichlorotitanium IV (DDCT) and its derivative, biscyclopentadienylditiocianatetitanium IV (BCDT), on the production of cytokines [interferon-gamma (IFN-γ), interelukin-1, interleukin (IL) 2, IL-4, and IL-10] by concanavalin A (Con A)-stimulated T cells obtained from Ehrlich ascites tumour (EAT)-bearing BALB/c mice. The treatment consisted of intraperitoneal (i.p) administration of 15 mg/kg/day DDCT for 2 days or 10 mg/kg/day BCDT for 3 days. We observed that the levels of IFN-γ, but not IL-2, were dramatically increased in the early phase of EAT development. With tumour evolution, however, a sharp and progressive decrease in the levels of both IFN-γ and IL-2 was found concomitantly to an enhancement in the levels of IL-10. Treatment of these mice with both titanocene compounds demonstrated that DDCT is more effective in modulating the cytokine imbalance induced by the tumour since it could prevent the early enhancement of IFN-γ, the late decline of IFN-γ and IL-2, and the increase in the IL-10. The administration of BCDT, in spite of preventing early IFN-γ enhancement and increase in IL-10, did not produce any change in the IL-2 levels and did not prevent the decline of IFN-γ levels during tumour evolution. Collectively, these results reveal that the ability of titanocenes to reverse tumour-induced immunosuppression and delay tumour growth is more evident in the DDCT compound, thus indicating that the substitution of the halides halogens by pseudohalogens, present in the molecular structure of BCDT, leads to a less effective antitumoral compound. [Copyright &y& Elsevier]

Aerva lanata whole plant was extracted with petroleum ether, methanol and acetone. The partially TLC-purified fraction (PEF) of petroleum ether extract was proved to be cytotoxic to Dalton''s lymphoma ascites (DLA), Ehrlich ascites (EA) and B16F10 cell lines in vitro. Since PEF was found to be more cytotoxic to DLA cell lines, it was used to study the pharmacological effect and its potential to reduce solid tumor induced by DLA cell lines in mice. The result indicated that PEF significantly reduced the development of solid tumor in mice. [Copyright &y& Elsevier]

Ninhydrin (2,2-dihydroxy-1, 3-indane dione)was evaluated for its antitumor and cytotoxicproperties in Ehrlich ascites carcinoma cell (EACCell)-bearing mice. The rationale behind this studyhas been mainly the literature reports of itscharacteristic interference with DNA synthesis andcalcium homeostasis. Antitumor activity was evaluatedfrom the total count and viability of EAC cells inaddition to their nucleic acid, protein, non-proteinsulfhydryls (NP-SH) and malondialdehyde (MDA)contents. The EAC cell-bearing animals were alsoobserved for the effect on their survival and bodyweight variations. In addition, the tumors grown atthe site of injection were evaluated forhistopathological changes. Ninhydrin treatments (5, 10and 20 mg/kg/day) abate the increase in body weightand advanced the duration of survival in EACcell-bearing mice. The results on histopathologicalinvestigations show retardation in tumor growth,decreased frequency of mitotic figures and hairfollicles and an increased necrosis in the tumor byninhydrin treatment. Our results on cytotoxicity,which demonstrated compression in the number of EACcells and their viability substantiate these data. Theresults of biochemical studies on EAC cells exhibit areduction in the levels of DNA, RNA, proteins andNP-SH with a subsequent increase in the concentrationsof MDA after ninhydrin treatment. Inhibition in tumorgrowth was dose dependently significant with the samedose regimen. The observed cytotoxic and antitumoractivity of ninhydrin was comparable tocyclophosphamide. The possible mode of action ofninhydrin-induced cytotoxic and antitumor activityappear to be due to its interference withmitochondrial function resulting in inhibition of DNAsynthesis, an effect that is being investigatedfurther. [ABSTRACT FROM AUTHOR]