Ehrlich Ascites Carcinoma In Mice Research Articles

Synthesis, structure, electrochemistry, and spectral characterization of bis-isatin thiocarbohydrazone metal complexes and their antitumor activity against ehrlich ascites carcinoma in swiss albino mice.

The synthesis, structure, electrochemistry, and biological studies of Co(II), Ni(II), Cu(II), and Zn(II) complexes of thiocarbohydrazone ligand are described. The ligand is synthesized starting from thiocarbohydrazide and isatin. It is evident from the IR data that in all the complexes, only one part of the ligand is coordinated to the metal ion resulting mononuclear complexes. The ligand coordinates essentially through the carbonyl oxygen of the isatin fragment, the nitrogen atom of the azomethine group, and sulfur atom after deprotonation to give five membered rings. NMR spectrum of the ligand shows only one set of signals for the aromatic protons, while the NH of isatin and NH of hydrazone give rise to two different singlets in the 11–14 ppm range. The formulations, [Cu(L)Cl]2O, [Cu(L)(CCOO)]2O, [Ni(L)Cl], [Ni(L)(CCOO)], [Co()], and [Zn()]2O are in accordance with elemental analyses, physical, and spectroscopic measurements. The complexes are soluble in organic solvents. Molar conductance values in DMF indicate the nonelectrolytic nature of the complexes. Copper complex displays quasireversible cyclic voltametric responses with Ep near 0.659 v and 0.504 v Vs Ag/AgCl at the scan rate of 0.1 V/s. Copper(II) complexes show a single line EPR signals. For the observed magnetic moment and electronic spectral data possible explanation has been discussed. From all the available data, the probable structures for the complexes have been proposed. The compounds synthesized in present study have shown promising cytotoxic activity when screened using the in vitro method and at the same time were shown to have good activity when tested using the Ehrlich ascites carcinoma (EAC) model. The antimicrobial screening showed that the cobalt complex possesses enhanced antimicrobial activity towards fungi.

Chemically Standardized Isolates from Cedrus deodara Stem Wood having Anticancer Activity

An isolate "CD lignan mixture" comprising lignans from stem wood of Cedrus deodara consisted of (-)-wikstromal (75 - 79%), (-)-matairesinol (9 - 13%) and benzylbutyrolactol (7 - 11%) and was studied for its in vitro cytotoxicity against human cancer cell lines. The in vivo anticancer activity of CD lignan mixture was studied using Ehrlich ascites carcinoma and colon carcinoma (CA-51) models in mice. Its effect was also studied on annexin V binding, intracellular caspases and DNA fragmentation to gain insight into the mode of action. In vitro cytotoxicity studies showed significant dose-dependent effects against several cancer cell lines from different tissues such as breast, cervix, neuroblastoma, colon, liver, and prostate at 10, 30 and 100 microg/mL. The IC (50) values varied from 16.4 ng/mL to 116.03 microg/mL depending on the cell line. Comparative data of IC (50) values of CD lignan mixture showed a synergistic effect in comparison to the individual molecules, i. e., (-)-matairesinol, (-)-wikstromol present in CD lignan mixture . CD lignan mixture had the most pronounced effect on CNS cell lines followed by colon. The tumor regression observed with Ehrlich ascites carcinoma and CA-51 was 53% and approximately 54%, respectively, when CD lignan mixture was given at 300 mg/kg, I. P. for nine days in the Ehrlich ascites carcinoma model and 400 mg/kg, I. P. for the same period in the CA-51 model. It was comparable with 5-fluorouracil at 22 mg/kg and 20 mg/kg, respectively. CD lignan mixture at 10, 30 and 100 microg/mL increased the percentage of annexin V positive HL-60 cells to 1.9 - 17.18% as compared to control (1.04%). In K562 cells CD lignan mixture at 10, 30 or 100 microg/mL and staurosporine (1 microM) showed 9.13%, 11.38%, 17.22% and 28.07% intracellular caspases activation, respectively. A distinct DNA laddering pattern was observed for treatment with the CD lignan mixture in HL-60, K562 (30 microg/mL and 100 microg/mL) and MOLT-4 cells (30 microg/mL) after 24 h incubation. DNA cell cycle analysis indicated that CD lignan mixture at 10, 30 and 100 microg/mL increased the content of hypodiploid (sub G(1) phase) cells when compared to control (2.55, 5.4 and 6.25% vs. 0.27%). The present study indicates that CD lignan mixture has cytotoxic potential against human cancer cell lines. It has the ability to induce tumor regression in vivo. It induces apoptosis as indicated by annexin V positive cells, induction of intracellular caspases, DNA fragmentation and DNA cell cycle analysis.

Antineoplastic Screening of Some Medicinal Plants Against Ehrlich Ascites Carcinoma in Mice

Antineoplastic Screening of Some Medicinal Plants Against Ehrlich Ascites Carcinoma in Mice

Pirarubicin is taken up by a uridine-transportable sodium-dependent concentrative nucleoside transporter in Ehrlich ascites carcinoma cells.

We evaluated the contribution of a nucleoside transporter (NT) consisting of an equilibrative NT (ENT) and a concentrative Na(+)/nucleoside cotransporter (CNT) to the uptake of THP and DOX by mouse Ehrlich ascites carcinoma cells. METHODS. Transport experiments were performed using a silicone layer method. The expression of CNT isoforms was confirmed by RT-PCR analysis. The effects of inhibition of the ENT inhibitors, nitrobenzylthioinosine (NBMPR) and nitrobenzylthioguanosine, on THP and DOX uptake by Ehrlich cells was negligible. THP uptake, but not DOX uptake, partially depended on an inwardly directed Na(+) gradient, and the uptake was inhibited by all the inhibitors of CNT examined. Furthermore, efflux of [(3)H]uridine from Ehrlich cells was stimulated by the addition of THP to the extracellular compartment, which was definitive evidence of CNT-mediated uptake of THP. The mRNA for CNT2, but not that for CNT3, was detected in Ehrlich cells, which is consistent with the characteristics of [(3)H]uridine uptake. In the cells, formycin B, a representative CNT2 ligand, had cis-inhibitory and trans-stimulatory effects on THP uptake. These results demonstrate that THP, but not DOX, is taken up into Ehrlich cells partially via a uridine-transportable CNT.

Synthesis and preliminary evaluation of gadolinium complexes containing sulfonamide groups as potential MRI contrast agents

Four DTPA and DOTA derivative ligands containing sulfonamide groups and their gadolinium complexes were prepared and characterized. Relaxivity studies showed that these gadolinium complexes possessed higher relaxation effectiveness than those of the corresponding ionic gadolinium complex Gd-DTPA and Gd-DOTA, respectively. In vitro cytotoxicity assay demonstrated that these gadolinium complexes have low cytotoxicity to the human liver cells (L-02). Magnetic resonance imaging (MRI) and experimental data of biodistribution in mice indicated that these gadolinium complexes containing sulfonamide groups could be used as the potential MRI contrast agents for Hepatoma (H 22) and Ehrlich ascites carcinoma (EAC) in mice and specific organs such as the liver and could be mostly excreted by the kidneys.

Antitumour Activity of Bauhinia variegata Against Ehrlich Ascites Carcinoma Induced Mice

The antitumour activity of ethanol extract of Bauhinia variegata (EBV) has been evaluated against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. A significant enhancement of mean survival time of EBV treated tumour bearing mice was found with respect to the control group. EBV treatment was found to enhance peritoneal cell counts. After 14 days of inoculation, EBV is able to reverse the changes in the haemotological parameters, protein and PCV consequent to tumour inoculation. Oral administration of EBV was effective in reducing solid tumour mass development induced by EAC cells. EBV was found to be a potent cytotoxic towards EAC tumour cells.

Tumour inhibitory activity of chicory root extract against Ehrlich ascites carcinoma in mice

The tumour-inhibitory effect of an ethanolic extract of chicory root was studied against Ehrlich ascites carcinoma in mice; significant results were obtained at doses from 300 to 700 mg/kg.

Synthesis, screening and quantitative structure–activity relationship (QSAR) studies of some glutamine analogues for possible anticancer activity

We described the syntheses, biological activities and QSAR studies of 36 new 5-n-substituted-2-(substituted benzenesulphonyl) glutamines 6–41 with different substitutions. These compounds were designed as structural analogues of most reactive amino acid, ‘glutamine’ (GLN), especially in the tumor cells. They present the new basic lateral chains at R5 position as well as different substitutions at 2′, 3′, 4′, and 5′ positions on the benzene ring. The synthesized compounds have been tested for antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice using percentage inhibition of tumor weight as inhibitory parameter. In order to elucidate the structural requirements for antitumor activity, quantitative structure–activity relationship (QSAR) studies have been performed using extra thermodynamic model of Hansch. QSAR equations showed that the electronic parameter (σ) on the aromatic ring system, steric parameter (Es) and to some extent Sterimol length of the substituent (L) on the aliphatic side chain correlate significantly with the antitumor activity. Resonance factor occupies the major electronic contribution on the aromatic ring system to the activity.

Syntheses, biological evaluation and QSAR study on antitumor activity of 1,5- N, N′-disubstituted-2-(substituted benzenesulphonyl) glutamamides

We have reported [unpublished data] the synthesis and QSAR of 5-substituted-2-(substituted benzenesulphonyl) glutamines which have shown the importance of steric factor on the aliphatic chain. N-Phthalyl isoglutamine, having the substitution at position 1 of the glutamic acid moiety, is the metabolite of recently approved thalidomide for different types of tumors by US FDA. Based on these, 36 new 1,5- N, N′-disubstituted-2-(substituted benzenesulphonyl) glutamamides were synthesized, as tools for further elucidation of the structural requirements for antitumor activity. All the synthesized compounds were tested for antitumor activity against Ehrlich Ascites Carcinoma (EAC) in Swiss albino mice using tumor weight as inhibitory parameter. Quantitative structure–activity relationship (QSAR) studies of these analogues revealed that the electron donating groups on the phenyl ring are found to be mandatory for the activity which was also proved by the negative coefficient of indicator parameter I 3, for NO 2 group on the phenyl ring. Molecular volume (MV) and steric factor at R 5 position also plays a role in ligand–receptor interactions.

Contribution of specific transport systems to anthracycline transport in tumor and normal cells.

Anthracycline antibiotics are very effective neoplastic agents widely used clinically. However, because of their many adverse effects (e.g. cardiotoxicity, leukopenia and alopecia), their clinical use has been limited. In order to minimize their adverse effects in clinical cancer chemotherapy, anthracyclines must be selectively transported into tumor cells. If there are differences in transport characteristics between tumor and normal cells, it should be possible to establish a strategy for selectively delivering anthracyclines to tumor cells on the basis of the differences. In human cultured leukemia HL60 cells, as tumor cells, and human fresh mononuclear cells, as normal cells, doxorubicin, pirarubicin, daunorubicin and idarubicin were incorporated via a common carrier-mediated system, but the carriers were different in the two cell types. In HL60 cells, it was indicated that a nucleoside transport system contributed, at least in part, to the transport of doxorubicin and pirarubicin, but not daunorubicin and idarubicin, and its contribution to pirarubicin transport was found in other tumor cells, i.e. mouse ovarian sarcoma M5076 and Ehrlich ascites carcinoma cells. On the other hand, in mononuclear cells, there was no involvement of a nucleoside transport system for the four anthracyclines examined. Therefore, we thought that with the modification of an anthracycline molecule as a substrate for the nucleoside transport system, the anthracycline could be delivered selectively to tumor cells.

Antineoplastic Activity of Cyanohydroxamic Acid (Sodium Salt) Against Ehrlich Ascites Carcinoma in Mice

Antineoplastic Activity of Cyanohydroxamic Acid (Sodium Salt) Against Ehrlich Ascites Carcinoma in Mice

Antineoplastic Activity of Chloroacetohydroxamic Acid in Combination with Bleomycin Against Ehrlich Ascites Carcinoma (EAC) in Mice

Antineoplastic Activity of Chloroacetohydroxamic Acid in Combination with Bleomycin Against Ehrlich Ascites Carcinoma (EAC) in Mice

Plumbagin, A Plant Naphthoquinone with Antitumor and Radiomodifying Properties

The tumor inhibitory and radiomodifying effects of plumbagin (Pl), a naphthoquinone isolated from Plumbago rosea, on mouse Ehrlich ascites carcinoma was studied. Tumor response was assessed by increase in life span (% ILS) and animal survival at 120 days. The acute LD 50 of plumbagin in normal mice was 9.4 mg/kg body weight. Single doses from 2 to 6 mg/kg Pl, given intraperitoneally (i.p.), produced inhibition of exponentially growing tumors. However, increases in dose above 3 mg/kg did not increase 120 day survival significantly over that produced by 3 mg/kg. Multiple dose treatment, starting from 24 h after tumor cell inoculation, showed that a total dose of 9 mg/kg, administered in three fractions of 3 mg/kg, once daily, gave the maximum %ILS and tumor free survival. Combination of radiation (RT, 7.5 Gy to the abdomen) after the first Pl dose (1-3mg/kg/fraction) synergistically increased mouse survival at 120 days. The tumor inhibitory effect was less pronounced when treatment was started at more advanced tumor stages, but combination of low dose fractions (2.5 or 3 mg/kg/fraction) with RT enhanced the %ILS and animal survival. Higher dose fractions in combination with radiation were not tolerated by the mice. DNA appears to be the likely target of Pl cytotoxicity; the mechanism of interaction of Pl + RT in enhancing tumor response is not clear.

A New Boron Compound (Guanidine Biboric Acid Adduct) as an Antitumour Agent against Ehrlich Ascites Carcinoma in Mice

The inhibitory effects of a new boron compound of guanidine biboric acid adduct (GB) and guanidium chloride (L₁) on the growth of ascites tumour in female Swiss mice were studied by monitoring the survival, tumour weight, tumour cell count, transplantability of Ehrlich ascites cells, precursor incorporation and the haematological parameters of the treated mice. 5-Fluorouracil, a known anticancer drug, was used as a positive control. The most important parameter was the survival time, which increased significantly when tumour-bearing mice were treated with the boron compound. Haematological parameters of the treated animals showed minimum toxic effects when boron was coupled with guanidine.

5-aminolaevulinic-acid-induced formation of different porphyrins and their photomodifications.

The relative amounts of 5-aminolaevulinic acid (ALA)-induced hydrophobic and hydrophilic porphyrins produced in normal mouse tissue and solid Ehrlich ascites carcinoma in mice were investigated as a function of added glucose, light irradiation and restricted blood flow to the tumour. Protoporphyrin IX (PpIX) is the predominant porphyrin produced from exogenous ALA in tissues that have viable mitochondria. However, under special conditions which seem to be connected with a reduced viability of the mitochondria, the formation of water-soluble porphyrins can be observed in vivo. Fluorescence maxima of the water-soluble porphyrins are located in the region between 615 and 625 nm. Irradiation can further lead to the formation of PpIX photoproduct(s), showing a fluorescence emission band at 676 nm. The photobleaching of PpIX in normal tissue and tumour tissue is different under restricted blood flow. ALA-induced PpIX can be observed in the normal blood stream, and can be linked to a slower photobleaching than in tissue with restricted blood flow.

Antitumor and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma in vivo.

The antitumor and radiosensitizing effects of withaferin A (WA), a steroidal lactone from Withania somnifera, was studied on Ehrlich ascites carcinoma in vivo. The acute LD50(14) for WA in Swiss mice was approximately 80 mg/kg. Twenty-four hours after i.p. inoculation of 10(6) tumor cells, WA was injected i.p. at different dose fractions (5 or 7.5 mg/kg x 8, 10 mg/kg x 5, 20 or 30 mg/kg x 2) with or without abdominal gamma irradiation (RT, 75. Gy) after the first drug dose. Increase in life span and tumor-free survival were studied up to 120 days. The drug inhibited tumor growth and increased survival, which was dependent on the WA dose per fraction rather than the total dose. Combination of RT with all the drug schedules increased tumor cure and tumor-free survival, the best effect seen after 2 fractions of 30 mg/kg each. In another experiment WA was given as 2 (40 mg/kg x 2), 3 (30 mg/kg x 3) or 4 (20 mg/kg x 4) fractions at 5, 7 or 10 days after tumor inoculation with or without RT after the first drug dose. At 7 and 10 days after inoculation the drug was effective only at 40 mg/kg x 2, but with RT 30 mg/kg x 3 produced an equal effect (20% survival) on 7 day old tumors.

In vivo growth inhibitory and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma.

Adult Swiss albino mice were inoculated intraperitoneally (i.p.) with 10 (6) Ehrlich ascites carcinoma cells. Twenty-four hours later they were given an i.p. injection of 10-60 mg/kg of withaferin A (WA), isolated from the roots of Withania somnifera. The tumor growth and tumor free animal survival were studied for up to 120 days. In another experiment 30 mg/kg WA was injected i.p. to mice at 1, 3 or 5 days after tumor cell injection with or without acute abdominal exposure to 7.5 Gy gamma radiation and the tumor growth and 120-day survival were studied. WA inhibited tumor growth and increased tumor free survival in a dose-dependent manner. The drug ED50 for 120-day survival was approximately 30 mg/kg body wt. Drug treatment before irradiation synergistically increased 120-day even in advanced tumors. A dose of 30 mg/kg seems to be optimum for combination with radiation.

Tea Plant Root Extract (TRE) as an Antineoplastic Agent

The antitumour effect of tea plant root extract (TRE) has been evaluated against Ehrlich ascites carcinoma (EAC) in Balb-C mice. Significant increases of survival times of the TRE-treated, tumour-bearing mice have been confirmed repeatedly with respect to the control group. TRE inhibited the tumour cell growth and reversed the changes of haematological parameters consequent to tumour inoculation.

Phosphate-activated glutaminase expression during tumor development

Changes in phosphate-activated glutaminase activities determined in intact cells and isolated mitochondria have been followed during mouse Ehrlich ascites carcinoma development. Glutaminase activities parallel the levels of poly(A) + RNAs encoding for the mitochondrial phosphate activated glutaminase. During the exponential growth phase, maximum activity was observed and the relative abundance of glutaminase mRNA significantly increased with regard to the stationary growth phase. The presented results show that tumor phosphate-activated glutaminase is subject to long-term regulation by differential gene expression.

Effects of Saffron on Vitamin A Levels and its Antitumour Activity on the Growth of Solid Tumours in Mice

AbstractInhibitory effects of saffron extract, a commonly used food spice, were studied against subcutane-ously inoculated solid Dalton's lymphoma ascites (DLA), Ehrlich ascites carcinoma (EAC) and Sarcoma-180 (S-180) tumours in mice. Oral administration of 100 mg/kg of the saffron extract significantly inhibited the growth of DLA and S-180 solid tumour by 87 and 41%, respectively. A dose of 150 mg/kg delayed the onset of tumour formation and inhibited further growth of a delayed Dalton's lymphoma ascites solid tumour by 80%. Chromium release cytotoxicity assay reflected the sensitivity of DLA and S-180 tumour cells to cytolysis (in vitro) in the presence of the extract. Estimation of serum vitamin A and β-carotene levels from S-180 tumour bearing mice treated with saffron extract indicated elevated serum levels of serum vitamin A and β-carotene. Chemical analysis of the antitumour compound from saffron extract indicated that crocin (a natural carotenoid) was responsible for the observed biological effect...