Ehrlich Ascites Tumor-bearing Mice Research Articles

Acylated chitosan anchored paclitaxel loaded liposomes: Pharmacokinetic and biodistribution study in Ehrlich ascites tumor bearing mice

Acylated chitosan (Myristoyl and Octanoyl) coated paclitaxel-loaded liposomal formulation was developed with an aim to overcome the cremophor EL related toxicities. They were evaluated for drug entrapment, in vitro drug release, and cytotoxicity and cell uptake behavior using A549 cells. The 99mTc radio-labeled formulations were also evaluated in vivo in Ehrlich Ascites Tumor (EAT) bearing mice for biodistribution and tumor uptake. The mean particle size of both coated and uncoated liposomal formulations was found to be in the range of 180–200 nm with high drug entrapment efficiency (>90% in case of uncoated liposomes and 80 ± 5% in case of coated liposomes). The uncoated liposomes displayed negative zeta potential (−10.5 ± 4.9 mV) whereas coated liposomes displayed positive zeta potential in the range of +21 to +27 mV. Slower drug release was observed in case of liposomes coated with acylated chitosans as compared to uncoated and native chitosan coated liposomes. All liposomal formulations were found less cytotoxic than paclitaxel injection (Celtax™, Celon Labs, India). In vitro cell uptake and intracellular distribution studies confirmed the cytosolic delivery of uncoated and coated liposomes. The myristoyl chitosan coated liposomal system (LMC) exhibited improved pharmacokinetic, biodistribution and tumor uptake characteristics over other formulations. These obtained results confirmed the potential application of acylated chitosn coated liposomal delivery systems (LMC) in tumor targeting of paclitaxel and other drugs.

Ehrlich ascites tumor-bearing mice treated with aqueous ethanol plant extract from <i>Euphorbia tirucalli</i> showed signs of systemic toxicity

Purpose: To evaluate the antitumor effect of a latex extract from Euphorbia tirucalli Linn. (Euphorbiaceae) and its toxicity. Methods: Aqueous ethanol and petroleum ether extracts were obtained through maceration. .Maximum tolerated dose was determined in healthy mice. Antitumor activity was measured in Ehrlich ascites tumor-bearing mice treated with the extract through intraperitoneal injection (62.5, 125 or 250 mg/kg) every 48 h (four doses). Efficacy was assessed by weight gain, abdominal circumference, volume of ascitic fluid and packed tumor cells, tumor cell viability and survival. Toxicity indicators were serum glucose, triglycerides, total proteins, activity of alanine and aspartate aminotransferases and mass of heart, spleen, kidney and liver. A hemolysis assay was also performed. Results: Doses of 62.5 and 125 mg/kg caused no antitumor activity, while 250 mg/kg dose reduced weight gain (3-fold), abdominal circumference and volume of ascitic fluid (> 50 %) and packed cells (50 %), but lowered tumor cell viability (40 %). However, mice treated with the extract survived for a shorter time than control mice. Furthermore, the 250 mg/kg dose caused cardiac atrophy, splenomegaly and fasting hyperglycemia. The extract caused hemolysis, and the half-maximal effective concentration (EC 50 ) was 1.6 (0.9 – 2.7) mg/mL. Conclusion: Euphorbia tirucalli extract inhibits Ehrlich ascites tumor in mice, but the therapeutic dose is also harmful to non-tumor tissues. Keywords: Euphorbia tirucalli , Ehrlich ascites tumor-bearing mice, Antitumor, Toxicity, Cardiac atrophy, Splenomegaly

In vivo inhibition of tumor progression by 5 hydroxy-1,4-naphthoquinone (juglone) and 2-(4-hydroxyanilino)-1,4-naphthoquinone (Q7) in combination with ascorbate

The purpose of the study was to obtain further in vivo data of antitumor effects and mechanisms triggered by juglone and Q7 in combination with ascorbate. The study was done using Ehrlich ascites tumor-bearing mice. Treatments were intraperitoneal every 24 h for 9 days. Control group was treated with excipient. Previous tests selected the doses of juglone and Q7 plus ascorbate (1 and 100 mg/kg, respectively). Samples of ascitic fluid were collected to evaluate carbonyl proteins, GSH and activity of antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Hypoxia inducible factor HIF-1α, GLUT1, proteins driving cell cycle (p53, p16 and cyclin A) and apoptosis (poly-ADP-polymerase PARP, Bax and Bcl-xL) were assessed by western blot. Tumor cells were categorized by the phase of cell cycle using flow cytometry and type of cell death using acridine orange/ethidium bromide. A glucose uptake assessment was performed by liquid scintillation using Ehrlich tumor cells cultured with 14C-deoxyglucose. Treatments caused increased protein carbonylation and activity of antioxidant enzymes and decreased levels of GSH, HIF-1α, GLUT1 and glucose uptake in tumor cells. They also caused increased number of tumor cells in G1, p53 and p16 activation and decreased cyclin A, but only when combined with ascorbate. Apoptosis was induced mostly when treatments were done with ascorbate, causing PARP and Bax cleavage, and increased Bax/Bcl-xL ratio. Juglone and Q7 in combination with ascorbate caused inhibition of tumor progress in vivo by triggering apoptosis and cell cycle arrest associated with oxidative stress, suppression of HIF-1 and uncoupling of glycolytic metabolism.

The Protective Effect of Royal jelly Against Doxorubicin-induced Renal Oxidative Stress, Histopathological and Immunohistochemiacal Alterations in Ehrlich Ascites Tumor Bearing Mice

ARTICLE INFO Article History In the present study, we investigated the potential protective effects of royal jelly against doxorubicin-induced nephrotoxicity in Ehrlich ascites tumor bearing mice. Adult male albino mice were randomly divided into eight groups: the control, royal jelly, doxorubicin, and royal jelly plus doxorubicin groups. Biochemical, oxidative stress, and histopathological and immunohistochemical methods were utilized for evaluation of the reno-toxicity. Blood was collected and analyzed for blood urea nitrogen (BUN), uric acid and creatinine. The renal samples were stored for the measurement of malondialdehyde (MDA), glutathione peroxidase (GSH) and superoxide dismutase (SOD) activities and processed for histopathological examinations. Administration of doxorubicin to mice bearing Ehrlich tumor induced a marked renal dysfunction, characterized with a significant increase in serum BUN, uric acid and creatinine concentrations, and they had higher renal MDA and decreased in GSH and SOD concentrations. In the groups that were feed on RJ in association with DOX, improvement was observed in some oxidative stress parameters and certain other biochemical, histopathological and immunohistochemical parameters. The royal jelly exerted significant protection against renal damage induced by doxorubicin through reduction of the elevated activities of serum renal functions. Moreover, royal jelly blocked doxorubicin-induced lipid peroxidation through decreasing the malondialdehyde formation. In conclusion, royal jelly has a capability to attenuate doxorubicin-induced nephrotoxicity.

Some genetic profiles in liver of Ehrlich ascites tumor-bearing mice under the stress of irradiation

Radiation therapy aims to kill cancer cells with a minimum of normal tissue exposure. In an attempt to define the molecular and biochemical changes associated with exposure to radiotherapy, the objective of the present study is to explore the effect of gamma (γ) irradiation on nuclear factor, erythroid 2 (NFE2), P53, stromelysin-1 (matrix metalloproteinase-3) (MMP3), BCL-2 and BAX genes expression in Ehrlich ascites carcinoma (EAC) bearing mice. Various biochemical parameters such as liver function, H2O2, B% and T% lymphocytes, total antioxidants and MDA were investigated to evaluate their usefulness as possible during cancer treatment with radiotherapy. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 0.5Gy. Sixty-four female mice, weighing 20–25g were used in this study and divided into three main groups. The first group served as control group, while the second were injected intraperitoneally with EAC then was subdivided into two groups, II A and II B. The latter one (group II B), the animals were exposed to a single dose of 0.5Gy whole body γ irradiation. The third main group, were irradiated with a single dose of 0.5Gy whole body γ irradiation. Blood and liver tissue samples were collected at 4, 24 and 96h post-irradiation. The gene expression levels in the livers of animals from each exposure group were compared individually with that of pooled sham-irradiated animals. MMP3 and NFE2 were overexpressed in liver samples of EAC group post 4, 24 and 96h of γ irradiation (IIB). On the other hand, P53 and BCL-2 genes were downregulated by using RT-PCR analysis post 4, 24 and 96h of γ irradiation (IIB). As well as, liver function and MDA were increased significantly in the γ - irradiation group (3rd group) when compared to control mice (1st group). Gamma irradiation 3rd group revealed increase in the level of T% and B% lymphocytes. According to the obtained results, both γ rays and time period alter the genes expression and most of the investigated biochemical parameters.

Addition of Propolis to Irinotecan Therapy Prolongs Survival in Ehrlich Ascites Tumor-Bearing Mice

We investigated possible synergistic action of anticancer drug Irinotecan (IRI) combined with ethanolic (EEP) and water-soluble (WSDP) derivate of propolis on Swiss albino mice injected with Ehrlich ascites tumor (EAT). For survival analysis mice were administered WSDP and EEP (100 mg/kg) daily for 3 consecutive days, beginning on 3rd day after EAT cell (1×10⁶) injection. IRI was administered at a dose of 50 mg/kg on days 1, 13, and 19. We simultaneously studied peripheral white blood cell count, cell types washed from the peritoneal cavity, functional activity of macrophages from peritoneal cavity, and the level of primary DNA damage in leukocytes, kidney, and liver cells using the alkaline comet assay. Three out of 9 mice per group survived the entire duration of the experiment (90 days) in groups treated with IRI combined with WSDP and EEP. All test components increased survival of mice by 7.53% to 231.54%. Combined treatment with IRI and/or WSDP and EEP significantly decreased percentage of tumor cells in the peritoneal cavity as compared to nontreated EAT-injected mice. All treated animals had significantly higher percentage of neutrophils in the peritoneal cavity in comparison to nontreated EAT-injected mice. We observed significantly higher value of DNA damage in leukocytes of mice treated with IRI and combination of IRI and/or WSDP and EEP as compared to nontreated EAT-injected mice, while the same treatment decreased DNA damage in kidney. Our results showed that addition of propolis to IRI treatment enhanced antitumor activity of IRI and prolongs survival in EAT-bearing mice, which definitely deserve further studies to clarify the possible mechanisms of antitumor actions of combined herb-drug treatments.

Anti-proliferative and angio-suppressive effect of Stoechospermum marginatum (C. Agardh) Kutzing extract using various experimental models.

BACKGROUND/OBJECTIVESAbundant consumption of seaweeds in the diet is epidemiologically linked to the reduction in risk of developing cancer. In larger cases, however, identification of particular seaweeds that are accountable for these effects is still lacking, hindering the recognition of competent dietary-based chemo preventive approaches. The aim of this research was to establish the antiproliferative potency and angiosuppressive mode of action of Stoechospermum marginatum seaweed methanolic extract using various experimental models.MATERIALS/METHODSAmong the 15 seaweeds screened for antiproliferative activity against Ehrlich ascites tumor (EAT) cell line, Stoechospermum marginatum extract (SME) was found to be the most promising. Therefore, it was further investigated for its anti-proliferative activity in-vitro against choriocarcinoma (BeWo) and non-transformed Human embryonic kidney (HEK 293) cells, and for its anti-migratory/tube formation activity against HUVEC cells in-vitro. Subsequently, the angiosuppressive activity of S. marginatum was established by inhibition of angiogenesis in in-vivo (peritoneal angiogenesis and chorioallantoic membrane assay) and ex-vivo (rat cornea assay) models.RESULTSMost brown seaweed extracts inhibited the proliferation of EAT cells, while green and red seaweed extracts were much less effective. According to the results, SME selectively inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but had a lesser effect on HEK 293 cells. SME also suppressed the migration and tube formation of HUVEC cells in-vitro. In addition, SME was able to suppress VEGF-induced angiogenesis in the chorio allantoic membrane, rat cornea, and tumor induced angiogenesis in the peritoneum of EAT bearing mice. A decrease in the microvessel density count and CD31 antigen staining of treated mice peritoneum provided further evidence of its angiosuppressive activity.CONCLUSIONSAltogether, the data underline that VEGF mediated angiogenesis is the target for the angiosuppressive action of SME and could potentially be useful in cancer prevention or treatment involving stimulated angiogenesis.

Synergistic Effects of Irinotecan and Flavonoids on Ehrlich Ascites Tumour-Bearing Mice

Swiss albino mice were given Ehrlich ascites tumour cells (1 × 10(6)) intraperitoneally. For survival analysis and tumour growth analysis, the mice were administered quercetin and naringin (100 mg/kg) daily for 3 consecutive days, beginning on the third day after intraperitoneal (i.p.) injection of Ehrlich ascites tumour cells (1 × 10(6)). Irinotecan was administered ip at a dose of 50 mg/kg on days 1, 13 and 19. For the analysis of cell types and differential count of cells present in the peritoneal cavity, peripheral whole-blood leucocyte count and the comet assay, the mice were treated therapeutically with quercetin and naringin (100 mg/kg) and irinotecan (50 mg/kg) daily for 3 consecutive days beginning on third day after i.p. injection of Ehrlich ascites tumour cells (1 × 10(6)). We observed the synergistic anti-tumour effect expressed as the median survival time of mice treated with naringin in combination with irinotecan. All test components inhibited tumour growth and increased lifespan of mice except quercetin. The total number of cells present in the peritoneal cavity of mice significantly decreased in all treatments except quercetin. Single irinotecan and irinotecan combined with naringin had the highest DNA-damaging potential on peripheral blood leucocytes and lowest primary DNA damage, both in the kidney and liver cells as measured by the alkaline comet assay. Our results showed enhanced anti-tumour activity of irinotecan in combined treatment with flavonoids to reduce the deteriorating reaction of cytostatic drugs.

Biodistribution of ascorbyl palmitate loaded doxorubicin pegylated liposomes in solid tumor bearing mice

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.

Preparation, characterization, and biodistribution of letrozole loaded PLGA nanoparticles in Ehrlich Ascites tumor bearing mice

Letrozole (LTZ) incorporated PLGA nanoparticles were prepared by solvent displacement technique and characterized by transmission electron microscopy, poly-dispersity index and zeta potential measurement. Radiolabeling of free LTZ and LTZ-loaded PLGA NPs was performed with technetium-99m with high labeling efficiency. The labeled complex showed good in vitro stability as verified by DTPA challenge test. The labeled complexes also showed significant in vivo stability when incubated in rat serum for 24 h. Biodistribution studies of 99mTc-labeled complexes were performed after intravenous administration in normal mice and Ehrlich Ascites tumor bearing mice. Compared to free LTZ, LTZ-loaded PLGA NPs exhibited significantly lower uptake by the organs of RES. The tumor concentration of LTZ-loaded PLGA NPs was 4.65 times higher than that of free LTZ at 4 h post-injection. This study indicates the capability of PLGA nanopartcles in enhancing the tumor uptake of letrozole.

Effects of Orally Administering Excessive Amounts of α-Linolenic Acid and Iron (II) on the n-3/n-6 Fatty Acid Composition of Tumor Cells and Serum in Ehrlich's Ascites Tumor-Bearing Mice and of Serum in Normal Mice

Effects of Orally Administering Excessive Amounts of α-Linolenic Acid and Iron (II) on the n-3/n-6 Fatty Acid Composition of Tumor Cells and Serum in Ehrlich's Ascites Tumor-Bearing Mice and of Serum in Normal Mice

Effect of a seashell protein Haishengsu on the immunological function of mice with Ehrlich ascites tumor

This study was designed to investigate the effect of a seashell protein Haishengsu (HSS) on the immuno logical function in mice with Ehrlich ascites tumor. Ehrlich ascites tumor-bearing mice were divided into three HSS groups (25, 50 and 100 mg/kg, i.v., respectively), cyclophosphamide (10 mg i.p.) and control group. The immunological function was assessed by measuring the phagocytizing capacity of the peritoneal macrophages and neutrophils, as well as the number of spleen hemolytic plaque-forming cells. The percentage of blood T-lymphocytes was also evaluated. The number and the percentage of phagocytizing macrophages and neutrophils in the 50 and 100 mg/kg HSS groups were higher than in the control and the cyclophosphamide groups (P < 0.01). The hemolytic plaque-forming cells in the three HSS groups (10.8 ± 1.2, 16.9 ± 3.9 and 25.3 ± 2.9, respectively), was greater than in the control (7.3 ± 1.4), or the cyclophosphamide group (0.33 ± 0.4) (all P < 0.01). In all HSS groups, the percentage of blood T3, T4 and T8 was higher than in the cyclophosphamide and the control group (all P < 0.01). We conclude that HSS has significant immune-modulating effect in mice with Ehrlich ascites tumor.

Chemotherapeutic potential of two gallic acid derivative compounds from leaves of Casearia sylvestris Sw (Flacourtiaceae)

Casearia sylvestris is a plant used in the treatment of several diseases, including cancer. Studies have shown that C. sylvestris presents an interesting antitumoral potential, due to the presence of casearins and some sesquiterpens with antitumoral activity. In this work, we tested the potential chemotherapeutic of two gallic acid-derived compounds isolated from C. sylvestris leaves: isobutyl gallate-3,5-dimethyl ether (IGDE) and methyl gallate-3,5-dimethyl ether (MGDE). We utilized two tumoral models: Ehrlich ascites tumor cells (EAT)/BALB/c mice and Lewis lung cancer cells (LLC1)/C57bl/6 mice. MGDE and IGDE increased the survival of mice inoculated with EAT cells and decreased the tumor volume in the LLC1 model, compared to control groups. Both compounds presented similar and low in vitro cytotoxicity against Ehrlich ascites tumor cells and did not present any significant toxicity against Lewis lung cancer cells. Since the direct in vitro activity against Ehrlich tumor and Lewis lung cancer cells was low, we investigated the effects of MGDE or IGDE treatment on the activity of total natural killer cells from Ehrlich ascites tumor-bearing mice, as a possible explanation for the mechanisms of these compounds in vivo. MGDE and IGDE improved NK cell cytotoxicity against Ehrlich ascites cells. As expected, tumor growth in non-treated mice markedly suppressed NK cell cytolysis while, IGDE completely reversed this effect, when mice were treated with 0.5 mg/kg dosages of these compounds for 4 days. The pharmacokinetic studies showed that IGDE remains in the organism for a long period of time, possibly explaining the higher compound efficiency.

Synthesis and Evaluation of 1-Benzhydryl-sulfonyl-piperazine Derivatives as Inhibitors of Tumor Growth and Tumor Angiogenesis of Mouse Ehrlich Ascites Tumor In Vivo

A series of novel 1-benzhydryl-sulfonyl-piperazine derivatives 3(a-e) were synthesized by nucleophilic substitution reaction of 1-benzhydryl-piperazine with different sulfonyl chlorides and were characterized by 1H NMR, LC/MS, FTIR and elemental analysis. In the present study, the compounds 3(a-e) exhibited in vivo inhibition of Ehrlich ascites tumor (EAT) cell growth and increased the Median Survival Time (MST) and %ILS of EAT bearing mice. Further treatment of derivatives in vivo resulted in reduction of EAT cell number and ascites formation. The efficacy of the derivatives to inhibit the angiogenesis in vivo was evaluated in tumor bearing mice peritoneum and chorio allantoic membrane (CAM) model. The compounds suppressed the blood vessel formation in vivo in mice peritoneum and in CAM. Among the compounds studied, 3e demonstrated highest tumor inhibitory and anti-angiogenic effects against mouse tumor. However, this phenomenon needs detailed investigation.

Evaluation of DNA damage in vivo induced by combined application of cisplatin and sevoflurane

The influence of the combined application of cisplatin and sevoflurane on a variety of cell types of healthy mice or mice bearing Ehrlich ascites tumour has been investigated in an in vivo study. The alkaline comet assay method was carried out on peripheral blood leucocytes, brain, liver, kidney and tumour cells of healthy mice or mice bearing Ehrlich ascites tumour. Groups of mice were treated intraperitoneally with cisplatin, exposed to sevoflurane or by combined treatment of sevoflurane after treatment with cisplatin for 3 consecutive days. The in vivo exposure to sevoflurane induced genotoxicity to all assayed cells. A strong synergistic genotoxic effect to peripheral blood leucocytes, liver and kidney cells was found in mice receiving both cisplatin and sevoflurane. In contrast, a decrease of the comet tail lengths of brain cells in the combined treatments was found as compared to cisplatin alone in both healthy (P < 0.001) and Ehrlich ascites tumour-bearing mice (P < 0.05), respectively. In addition, Ehrlich ascites tumour cells of mice treated with combined treatments showed a decrease in tail lengths (P < 0.001). These findings indicate an antagonistic effect of combined treatments. Treatment of mice with cisplatin and sevoflurane induced genotoxic effect in peripheral blood leucocytes, liver, kidney, brain and Ehrlich ascites tumour cells; synergistic effect of combined treatments was expressed in all cells but brain and Ehrlich ascites tumour cells.

Comparative studies of the effects of Tabebuia avellanedae bark extract and β-lapachone on the hematopoietic response of tumour-bearing mice

The effects of Tabebuia avellanedae (TACE), traditionally prescribed in the treatment of cancer, and the naphtoquinone β-lapachone (β-lap) on the growth and differentiation of granulocyte and macrophage progenitor cells (CFU-GM) were studied in Ehrlich ascites tumour-bearing mice. Myelosuppression concomitant with increases in spleen CFU-GM and in serum colony-stimulating activity (CSA) were observed in these animals. Treatment with TACE (30–500 mg/kg) and β-lap (1–5 mg/kg) reversed these effects in a dose-dependent manner. The optimal biologically active doses of 120 mg/kg TACE and 1 mg/kg β-lap prolonged life span of tumour-bearing mice, both producing the same rate of extension in the duration of survival. Toxic manifestations were produced by the higher doses of β-lap in normal and tumour-bearing mice. In spite of similarities between treatments, TACE concentrations used to treat the animals presented no traces of β-lap, as measured by TLC and HPLC analyses. Our findings suggest that the antitumour effect of TACE and β-lap, acting synergistically with other factors, such as specific cytokines, may result from enhanced macrophage activation against tumour cells. In addition, it is clear from our results that hematopoietic disorders produced by tumours are an important pathological condition that must be considered in drug development.

Development and characterization of hyaluronic acid–anchored PLGA nanoparticulate carriers of doxorubicin

A novel hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide) (HA-PEG-PLGA) copolymer was synthesized and characterized by infrared and nuclear magnetic resonance spectroscopy. The nanoparticles of doxorubicin (DOX)-loaded HA-PEG-PLGA were prepared and compared with monomethoxy(polyethylene glycol) (MPEG)-PLGA nanoparticles. Nanoparticles were prepared using drug-to-polymer ratios of 1:1 to 1:3. Drug-to-polymer ratio of 1:1 is considered the optimum formulation on the basis of low particle size and high entrapment efficiency. The optimized nanoparticles were characterized for morphology, particle size measurements, differential scanning calorimetry, x-ray diffractometer measurement, drug content, hemolytic toxicity, subacute toxicity, and in vitro DOX release. The in vitro DOX release study was performed at pH 7.4 using a dialysis membrane. HA-PEG-PLGA nanoparticles were able to sustain the release for up to 15 days. The tissue distribution studies were performed with DOX-loaded HA-PEG-PLGA and MPEG-PLGA nanoparticles after intravenous (IV) injection in Ehrlich ascites tumor–bearing mice. The tissue distribution studies showed a higher concentration of DOX in the tumor as compared with MPEG-PLGA nanoparticles. The in vivo tumor inhibition study was also performed after IV injection of DOX-loaded HA-PEG-PLGA nanoparticles up to 15 days. DOX-loaded HA-PEG-PLGA nanoparticles were able to deliver a higher amount of DOX as compared with MPEG-PLGA nanoparticles. The DOX-loaded HA-PEG-PLGA nanoparticles reduced tumor volume significantly as compared with MPEG-PLGA nanoparticles.

In vivo growth inhibitory and anti-angiogenic effects of synthetic novel dienone cyclopropoxy curcumin analogs on mouse Ehrlich ascites tumor

In the present study, four novel dienone cyclopropoxy curcumin analogs 1a– 4a were synthesized by nucleophillic substitution reaction with cyclopropyl bromide. The tumor inhibitory and anti-angiogenic effects of the synthetic compounds were studied on mouse Ehrlich ascites tumor (EAT) in vivo. The compounds 1a– 4a increased the life span (% ILS) of EAT bearing mice with corresponding significant reduction in ascites volume and cell number and induced apoptotic bodies in EAT cells. Anti-angiogenic studies of the compounds demonstrated significant reduction of microvessel density (MVD) in the peritoneum wall sections of mice and induced avascular zone in CAM model. Our findings demonstrate that the tumor growth inhibitory effects of synthetic dienone cyclopropoxy curcumin analogs 1a– 4a could be mediated by promoting apoptosis and inhibiting tumor angiogenesis. However, the compounds need to be explored further to assess its clinical relevance.

Chemotherapeutic potential of the volatile oils from Zanthoxylum rhoifolium Lam leaves

In this work, the anti-tumor properties of the volatile oil from Zanthoxylum rhoifolium Lam leaves and some terpenes (α-humulene, β-caryophyllene, α-pinene and β-pinene) were investigated in vitro and in vivo using the Ehrlich ascites tumor model. Treatment of Ehrlich ascites tumor-bearing mice with 20 mg/kg of the volatile oil and β-caryophyllene for 4 days has significantly increased survival, whereas administration of α-humulene, α-pinene and β-pinene were ineffective in affording protection. Volatile oil and β-caryophyllene exhibited little direct activity against Ehrlich tumor cells in vitro, while α-humulene, α-pinene and β-pinene did not such activity. Investigation of the effects of the volatile oil (and terpenes) treatment on total natural killer cells (NK cell) activity from tumor-bearing mice as a possible mechanism of these compounds in vivo revealed that volatile oil and β-caryophyllene significantly improved NK cell cytotoxicity against YAC-1, a Moloney virus-induced mouse T-cell lymphoma of A/SN origin and Ehrlich ascites cells. As expected, tumor growth in non-treated mice markedly suppressed NK cell cytolysis while the volatile oil and β-caryophyllene reversed this effect when mice were treated with 20-mg/kg dosages of these compounds for 4 days. Summing up, volatile oil exhibits anti-tumor efficacy and significative immunomodulatory action in vivo, which may be related to β-caryophyllene associated to the synergism of other natural compounds presented in volatile oil from Z. rhoifolium Lam leaves.

99mTc-YIGSR as a receptor tracer in imaging the Ehrlich ascites tumor-bearing mice as compared with 99mTc-MIBI

The validity of (99m)Tc-YIGSR, a novel receptor radio-tracer, in imaging the Ehrlich ascites tumor was evaluated. YIGSR, a pentapeptide of laminin, was labeled with (99m)Tc by using a bifunctional chelator S-Acetly-NH(3)-MAG(3). The MIBI was labeled with (99m)Tc by following the kit instruction. The mice of tumor group were intravenously injected 1-2 mCi of (99m)Tc-YIGSR or (99m)Tc-MIBI via caudal vein, immobilized and imaged under a Gamma camera. The same procedure was performed in mice of blockade group, in which the unlabeled YIGSR was previously injected to block the receptor-recognition sites, and inflammation group serving as control. The reverse-phase Sep-Pak C(18) chromatogram was found to have an essentially complete conjugation between YIGSR and S-Acetly-NH(3)-MAG(3). The conjugated YIGSR could be radio-labeled successfully with (99m)Tc at room temperature and neutral pH, with a radio-labeling yield of 62%. Without the chelator S-Acetly-NH(3)-MAG(3), the YIGSR was labeled with (99m)Tc at an efficiency of 4%. The imagological study revealed obvious tumor accumulation of (99m)Tc-YIGSR 15 min after the injection, and the uptake peaked after 3 h with a tumor-to-muscle ratio (T/M) of 11.36. The radio-tracer was slowly cleared up and resulted in a T/M of 3.01 at the 8th h after the injection. As for blocked group, the tumor uptake of radiotracer was significantly lower, with the highest T/M being 4.61 after 3 h and 0.89 after 8 h. The T/M was 3.72 at the 3rd h and 1.29 at the 8th h after the (99m)Tc-YIGSR injection in the inflammatory group. The T/M was significantly higher in tumor group than in inflammatory group or control group (P<0.001). In the 99mTc-MIBI group, the T/M was 1.40 at the 3rd h and 0.55 at the 8th h after the injection, which showed a significant difference as compared with (99m)Tc-YIGSR (P<0.001). It is concluded that YIGSR can be successfully radiolabelled by using S-Acetly-NH(3)-MAG(3). (99m)Tc-YIGSR has many advantages in tumor imaging, such as quick and clear visualization, high sensitivity and specificity, and satisfactory target/non-target ratio (N/NT). It promises to be tumor radio-tracer.