Tumor Bearing Swiss Albino Mice Research Articles

Synthesis, 99mTc-labeling, in-vivo study and in-silico investigation of 6-amino-5-[(bis-(2-hydroxy-ethyl)-amino]methyl]2-methyl pyrimidin-4-ol as a potential probe for tumor targeting

This study aimed to synthesize a new pyrimidine derivative with a good synthesis yield of 87% to act as a new cancer marker after radiolabeling with Tc-99m in a high radiochemical yield of 92.3%. In-vivo study in tumor-bearing Swiss albino mice model revealed promising data with high uptake in cancer. Docking study showed good binding interactions of the radiosynthesized complex at the binding site. In conclusion, this novel complex could be a potential probe for cancer targeting.

TREATMENT WITH FERULIC ACID AMELIORATED CISPLATIN‑INDUCED NEPHROTOXICITY AND OXIDATIVE STRESS IN TUMOR BEARING MICE

Cisplatin (Cis) is one of the most widely used cytotoxic therapeutic agents for the treatment of cancer. Overdose of the drug resulted in various side effects of genotoxicity and nephrotoxicity. The toxicity of the drug has been attributed to the generation of oxidative free radicals. The current study aims to explore the effect of Ferulic acid (FA) in ameliorating Cis-induced renal toxicity in tumor bearing Swiss albino mice. Nephrotoxicity was induced in tumor bearing mice by a single dose of Cis (12mg/kg, i.p). Post administration of FA was carried out (100 mg/kg p.o and 200 mg/kg p.o) one hour after Cis administration. Toxicity was measured by analyzing the amount of serum urea, creatinine, and antioxidant status of renal and tumor tissues. Treatment of cisplatin-administered tumor animals with the FA could prevent the drug-induced oxidative damage as evidenced by the decreased levels of lipid peroxidation and enhanced activities of the antioxidants in the renal tissues. The treatment also protected the renal tissues from the toxic effects of Cis by reducing the levels of serum urea and creatinine. FA protected the renal tissues, whereas it enhanced the anticancer efficacy of Cis in tumor tissues. The histopathological observations support that ferulic acid has a protective effect against Cisplatin-induced nephrotoxicity and can be used to improve the chemotherapeutic index of Cisplatin for cancer treatment.

Gold(III) complex from pyrimidine and morpholine analogue Schiff base ligand: Synthesis, characterization, DFT, TDDFT, catalytic, anticancer, molecular modeling with DNA and BSA and DNA binding studies

New gold(III) complex, [AuL2]Cl3 was synthesized from (2-(4-morpholinobenzylidene)-1-(4-(trifluoromethyl)pyrimidin-2-yl)hydrazine) and characterized by analytical and miscellaneous spectral methods. These results show that Au(III) complex has square planar geometry. Density functional theory (DFT) calculations have been done to understand the electronic structure of the Au(III) complexand free ligand while time dependent density functional theory (TDDFT) calculations have been employed to compute absorption spectra of ligand and Au(III) complex. Antimicrobial results suggest that ligand and complex have been inhibited the E. coli bacteria (13 mm) and C. albicans fungi (16 mm) than other microbes. Antioxidant results exhibit the ligand and complex has enhanced scavenging activities against several free radicals. In vitro anticancer activities of cisplatin, ligand and complex have been explored by MTT assay against various human cancer cell lines (breast-MCF-7, liver-HepG2, cervical-HeLa, lung-A549) and one normal cell line (NHDF- normal human dermal fibroblasts). The results show that complex has low IC50 values against cancer cell lines (20.6 ± 0.98 μg/mL, MCF-7; 22.68 ± 1.13 μg/mL, HepG2; 32.00 ± 1.60 μg/mL, HeLa; 33.19 ± 1.66 μg/mL, A549) than ligand. Moreover, complex has ten times least toxic activity (109.65 ± 5.48 μg/mL) on NHDF cell line as compared to cisplatin (10.28 ± 0.51 μg/mL). Based on the least toxic activity of complex has been further discovered by in vivo anticancer study using Ehrlich Ascites Carcinoma (EAC) tumor bearing Swiss albino mice. DNA interactions of ligand and complex have been studied by electronic absorption, fluorescence, viscometric and cyclic voltammetic methods. The results suggest that ligand and complex binds with CT-DNA through an intercalative interaction. Further confirm the nature of interaction between ligand and Au(III) complex towards DNA and BSA protein, molecular docking analysis has been carried out. These results reveal that Au(III) complex shows greater binding ability towards DNA and BSA than the ligand.

Benzoin Thiosemicarbazone Inhibits Growth and Triggers Apoptosis in Earlich Ascites Carcinoma Cells through an Intrinsic Pathway

Anticancer drug development is now an emerging field of research all over the world. In this study we attempt to synthesize a novel, simple, inexpensive and safe chemical agents Benzoin thiosemicarbazone (BTSC) and studied against Ehrlich Ascites Carcinoma (EAC) cells bearing Swiss Albino mice by monitoring in vivo tumor cell growth inhibition, survival time of tumor bearing swiss albino mice. MTT colorimetric assay was done to assess the in vitro effect of the test compound. The intrinsic apoptotic pathway induced by BTSC was evidenced by p53 or tumor protein, B-cell lymphoma 2 (BCL-2), B-cell lymphoma extra-large (BCL-xL), BCL-2 associated X protein (BAX), cleavage of caspase-9 and caspase-3 and poly-ADP ribose polymerase (PARP-1). Reactive oxygen species (ROS) generation after BTSC treatment was determined by 2´, 7´- dicholorodihydrofluorescein diacetate (DCFH-DA) staining. The compound was found to possess pronounced anticancer effect. Maximum cell growth inhibition, enhancement of life span was found 73.53% and 52.17% at the dose of 8 mg/kg (i.p) respectively. The induction of apoptosis by BTSC occurred through an ROS-dependent mitochondria-mediated intrinsic pathway rather than an extrinsic pathway, and was regulated by the BCL-2 protein family. The compound exerted a potent antitumor effect toward Ehrlich ascites carcinoma cells through the induction of apoptosis via an intrinsic pathway. Thus, this study provides evidence to carry out further researches in a way to formulate novel anticancer drugs.

EVALUATION OF ANTICANCER POTENTIAL OF ETHANOLIC EXTRACT OF ALANGIUM SALVIFOLIUM LEAVES IN ANIMAL MODELS

Objective: The present study aims to evaluate the anticancer potential of ethanolic extract of Alangium salvifolium leaves (EASL) against Ehrlich ascites carcinoma (EAC) in animal model.
 Methods: The ethanolic extract of A. salvifolium was prepared by continuous method using Soxhlet apparatus. Phytochemical analysis of EASL was conducted. Anticancer activity of the extract was evaluated by EAC model in Swiss albino mice. EASL was administered at the doses of 100 and 200 mg/kg body weight once a day orally for 14 days, after 24 h of tumor inoculation.
 Results: A. salvifolium leaves extract treatment produced significant decrease in tumor volume and body weight, and increase in total and non-viable cell count, along with elevated life span of EAC-bearing mice. The EASL exhibited potent dose-dependent antitumor activity. Further, the altered hematological parameters such as red blood cells, hemoglobin, and white blood cells levels as well as biochemical parameters such as serum glutamic oxaloacetic transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, albumin, and total protein levels in EAC mice were significantly (p<0.05) regained following treatment with EASL. The anticancer potential of EASL can be attributed to the presence of phenols and flavonoids.
 Conclusion: Results suggest that EASL possesses significant anticancer activity against EAC tumor-bearing Swiss albino mice.

In vivo anticancer activities of Ni (II)-Benzoin thiosemicarbazone complex [Ni(BTSC)2] against ehrlich ascites carcinoma cells

Cancer is a class of diseases in which a group of cells display uncontrolled growth, invasion and sometimes metastasis. In order to find out a new anticancer drug, Ni(II) complex with benzoin thiosemicarbazon was synthesized and characterized. Anticancer activities of Ni(BTSC)2 2 2 has been studied against Ehrlich Ascites Carcinoma (EAC) cells in Swiss albino mice by monitoring tumor cell growth inhibition, tumor weight measurement, survival time of tumor bearing Swiss albino mice. Hematological parameters were also studied in both normal and EAC bearing treated mice. The results were compared with those obtained with a standard anticancer drug bleomycin and the compound was found to possess pronounced anticancer effect. Maximum cell growth inhibition was found to be 77.15% after treatment with Ni(BTSC)2 at the dose of 8 mg/kg (i.p). About 69.56% enhancement of life span was found at 8 mg/kg (i.p).With the same dose Ni(BTSC)2 reduced the tumor weight by 52.17% at day 20. The hematological parameters (WBC, RBC, hemoglobin content and differential counts) were found to be significantly changed as compared to those of the normal mice. These parameters restored more or less towards normal when treated with the test compound.J. bio-sci. 23: 77-88, 2015

Folic Acid and Trastuzumab Functionalized Redox Responsive Polymersomes for Intracellular Doxorubicin Delivery in Breast Cancer.

Redox responsive biodegradable polymersomes comprising of poly(ethylene glycol)-polylactic acid-poly(ethylene glycol) [PEG-s-s-PLA-s-s-PLA-s-s-PEG] triblock copolymer with multiple disulfide linkages were developed to improve intracellular delivery and to enhance chemotherapeutic efficacy of doxorubicin in breast cancer with minimal cardiotoxicity. Folic acid and trastuzumab functionalized monodispersed polymersomes of size ∼150 nm were prepared by nanoprecipitation method while achieving enhanced doxorubicin loading of ∼32% in the polymersomes. Multiple redox responsive disulfide linkages were incorporated in the polymer in order to achieve complete disintegration of polymersomes in redox rich environment of cancer cells resulting in enhanced doxorubicin release as observed in in vitro release studies, where ∼90% doxorubicin release was achieved in pH 5.0 in the presence of 10 mM glutathione (GSH) as compared to ∼20% drug release in pH 7.4. Folic acid and trastuzumab mediated active targeting resulted in improved cellular uptake and enhanced apoptosis in in vitro studies in breast cancer cell lines. In vivo studies in Ehrlich ascites tumor bearing Swiss albino mice showed enhanced antitumor efficacy and minimal cardiotoxicity of polymersomes with ∼90% tumor regression as compared to ∼38% tumor regression observed with free doxorubicin. The results highlight therapeutic potential of the polymersomes as doxorubicin delivery nanocarrier in breast cancer therapy with its superior antitumor efficacy and minimal cardiotoxicity.

Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect

PurposeThe normal metabolite methylglyoxal (MG) specifically kills cancer cells by inhibiting glycolysis and mitochondrial respiration without much adverse effect upon normal cells. Though the anticancer property of MG is well documented, its gradual enzymatic degradation in vivo has prompted interest in developing a nanoparticulate drug delivery system to protect it and also to enhance its efficacy.Materials and methodsMG-conjugated chitosan nanoparticles (Nano-MG) were prepared by conjugating the carbonyl group of MG with the amino group of chitosan polymer (Schiff’s base formation). Nano-MG were characterized in detail using the dynamic light scattering method, zeta potential measurement, Fourier transform infrared spectroscopy, and transmission electron microscopic analysis. Amount of MG anchored to Nano-MG, stability of Nano-MG, and in vitro release of MG from Nano-MG were estimated spectrophotometrically. Ehrlich ascites carcinoma (EAC) cells, human breast cancer cell line HBL-100, and lung epithelial adenocarcinoma cell line A549 were used as test systems to compare Nano-MG with bare MG in vitro. Cytotoxicity to EAC cells was evaluated by the trypan blue dye exclusion test, and cell viability of HBL-100 and A549 cells were studied using 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis of HBL-100 cells was assessed by flow cytometry and confocal microscopy. In vivo studies were performed on both EAC cells inoculated and also in sarcoma-180-induced solid tumor-bearing Swiss albino mice to assess the anticancer activity of Nano-MG in comparison to bare MG with varying doses, times, and administrative routes.ResultsFourier transform infrared spectroscopy revealed the presence of imine groups in Nano-MG due to conjugation of the amino group of chitosan and carbonyl group of MG with diameters of nanoparticles ranging from 50–100 nm. The zeta potential of Nano-MG was +21 mV and they contained approximately 100 μg of MG in 1 mL of solution. In vitro studies with Nano-MG showed higher cytotoxicity and enhanced rate of apoptosis in the HBL-100 cell line in comparison with bare MG, but no detrimental effect on normal mouse myoblast cell line C2C12 at the concerned doses. Studies with EAC cells also showed increased cell death of nearly 1.5 times. Nano-MG had similar cytotoxic effects on A549 cells. In vivo studies further demonstrated the efficacy of Nano-MG over bare MG and found them to be about 400 times more potent in EAC-bearing mice and nearly 80 times more effective in sarcoma-180-bearing mice. Administration of ascorbic acid and creatine during in vivo treatments augmented the anticancer effect of Nano-MG.ConclusionThe results clearly indicate that Nano-MG may constitute a promising tool in anticancer therapeutics in the near future.

Synthesis, characterization and biological evaluation of a novel vanadium complex as a possible anticancer agent

Chemotherapeutics are the sole treatment modality for cancer patients at advanced condition. In the pursuit of getting an efficient, selective and non toxic anticancer agent that has not been discovered yet, we rationally synthesized a vanadium complex with a Schiff base ligand N-(-2-hydroxyacetophenone) glycinate. Characterization of the synthesized complex VO(NG)2, was carried out with the help of various spectroscopic means. The complex proved to be a broad spectrum anticancer agent with significantly less toxicity towards normal cells as evident from cell viability assay. Furthermore, VO(NG)2 treatment increased the life-span of ascitic and solid tumor bearing Swiss albino mice and did not show any significant symptomatic sub acute toxicity on normal Swiss albino mice.

2-[5-Selenocyanato-pentyl]-6-amino-benzo[de]isoquinoline-1,3-dione inhibits angiogenesis, induces p53 dependent mitochondrial apoptosis and enhances therapeutic efficacy of cyclophosphamide.

The present study embodies a detailed investigation of the chemoenhancement property of a synthetic organoselenium compound, 2-[5-selenocyanato-pentyl]-7-amino benzo[de]isoquinoline-1,3-dione (ANOS) in tumor bearing Swiss albino mice. The results accumulated from this study illustrated that the administration of ANOS significantly potentiated the therapeutic efficacy of cyclophosphamide by reducing the tumor burden and chemotherapy induced toxicity in the host. Ability of ANOS in inducing apoptosis and inhibiting angiogenesis was thought to be the crucial effecter for enhancing the therapeutic efficacy of cyclophosphamide. Fluorescence microscopic study revealed that ANOS was capable of penetrating tumor cells and distributed in the subcellular compartments. We showed that ANOS-induced apoptosis, as evidenced by the TUNEL assay and cleavage of poly(ADP-ribose) polymerase (PARP), involved ROS production and DNA damage in tumor cells. ROS production subsequently activated p53 phosphorylation at Ser-15. This in turn activated cytochrome c (cyt c) release from mitochondria via Bcl-2 and Bax. Finally activation of caspase 3 led to PARP cleavage and apoptosis. These results suggested that p53 dependent mitochondrial pathway was playing an important role in ANOS induced apoptosis of tumor cells. Administration of ANOS also resulted in significant improvement of tumor vasculature and sprouting of the peritoneal cavity along with the normalization of MMP-9 level in serum and ascites fluid of tumor bearing mice. This potential antiangiogenic activity of ANOS also facilitated the therapeutic efficacy of the combination therapy. Furthermore, ANOS significantly suppressed cyclophosphamide-induced liver, hematopoietic and genetic damages. A concomitant decrease in drug-induced toxicity by ANOS might also have enhanced the efficacy of cyclophosphamide by improving the intrinsic defense machineries of the host.

Antitumorigenic Potential of Linalool Is Accompanied by Modulation of Oxidative Stress: An In Vivo Study in Sarcoma-180 Solid Tumor Model

Coriander, used as a common food seasoning, contains linalool as the main constituent of its essential oil. In this study, we tested the effect of linalool vis-à-vis that of a conventional chemotherapeutic drug, cyclophosphamide, against solid S-180 tumor-bearing Swiss albino mice. Tumor volume, cell count, cell cycle phase distribution, apoptosis, and proliferation markers indicate that linalool has potent antitumor activity. In vitro and in vivo data suggest that induction of oxidative stress might be responsible for the anticancer effect of linalool. However, interestingly, unlike cyclophosphamide, linalool did not induce myelosuppression or hepatotoxicity in mice as evident from bone marrow cell count, status of hepatic oxidative stress/antioxidant enzymes, and histopathology. Thus, linalool exerted prooxidant effect in tumor tissue and an antioxidant effect in liver. This is also supported by the expression of Nrf-2 and p21, which are considered to be important players in response to oxidative stress. Moreover, administration of linalool modulated the proliferation of spleen cells in tumor-bearing mice challenged with lipopolysaccharide. Finally, the detection of linalool in sera and tumor tissues by HPLC confirmed its bioavailability. In conclusion, linalool showed differential cytotoxicity towards tumor and normal cells in contrast to cyclophosphamide, which is uniformly toxic to both.

Preventive effect of ethanol extract of Alpinia calcarata Rosc on Ehrlich's ascitic carcinoma cell induced malignant ascites in mice

Objective To explore cytotoxic activity of ethanol extract of Alpinia calcarata Rosc (EEAC) rhizome against Ehrlich ascites carcinoma (EAC) tumor bearing Swiss Albino mice. Methods In the present study, its anti-neoplastic activity has been studied by monitoring parameters like tumor weight measurement, survival time, tumor cell growth inhibition, haematological characteristics etc. Results It was found that EEAC at dose 8 mg/kg/day ( i.p.) significantly decreased tumor weight (62.0%; P <0.01), increased life span (70.25%; P <0.01) and reduced tumor cell growth rate (85.7%; P <0.01) in comparison to those of EAC bearing mice. The plant extract also improved the depleted haematological parameters like RBC, WBC, Hb%, differential counts ( e.g. lymphocytes, neutrophils, monocytes etc) of EAC bearing mice towards normal. The host toxic effects were not very high and recovered gradually towards normal within a few days after treatment. Conclusions EEAC exhibits potent in vivo cytotoxic activity against EAC tumor bearing Swiss Albino mice. So, the plant can be considered as a probable new source of antitumor agents.

D-Aminoacid Oxidase-Fe&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt;O&amp;lt;sub&amp;gt;3&amp;lt;/sub&amp;gt; Nanoparticle Complex Mediated Antitumor Activity in Swiss Albino Mice

D-Aminoacid oxidase (DAO) was isolated from fresh porcine kidney; its cytotoxic potential was studied under in vitro and in vivo conditions. The isolated DAO was complexed with Fe2O3 nanoparticles and its potential as an oxidation therapeutic agent was analysed. The ability of the complex in eliciting H2O2 mediated cytotoxicity was studied on Dalton’s lymphoma ascites cells (DLA). The induction of apoptosis in DLA cells by Fe2O3-DAO complex was studied by morphological examination and alkaline single cell gel electrophoresis (comet assay). The antitumor activity of the complex was investigated by oral administration of the complex and the substrate D-alanine to tumor bearing Swiss albino mice and by targeting the complex to the tumor site, using an externally applied magnetic field. Fe2O3-DAO along with D-alanine showed remarkable cytotoxicity in a substrate concentration-dependent manner. Both morphological examination and comet assay revealed that Fe2O3-DAO/D-alanine induced apoptosis. Oral administration of Fe2O3-DAO and D-alanine along with magnetic targeting significantly suppressed tumor growth in mice. The present report provides the first evidence for the promising application of enzyme bound nanoparticles for targeted oxidation therapy.

Enhanced antitumor activity of irinotecan combined with propolis and its polyphenolic compounds on Ehrlich ascites tumor in mice

The effects of the anticancer drug irinotecan combined with ethanolic extract of propolis (EEP), a water-soluble derivate of propolis (WSDP), quercetin and naringin on the growth of Ehrlich ascites tumor (EAT) and the life span of tumor-bearing Swiss albino mice were studied. Test components were given to mice intraperitoneally ( i.p.) at doses of 100 mg kg −1 for three consecutive days before the i.p. injection of EAT cells (1 × 10 6). Irinotecan was administered i.p. at dose of 50 mg kg −1 on days 1, 13, and 19 after tumor cell inoculation. The results clearly demonstrate the synergistic action of irinotecan and EEP on survival time. These results suggest that clinical trials using a propolis preparation EEP combined with irinotecan may be beneficial in maximizing antitumor activity and minimizing post-chemotherapeutic reactions to the cytostatic drug.