Ehrlich Ascites Carcinoma Tumor Research Articles

Anti-tumoral Immunity and Chemo-preventive Effectiveness of Herbal Extracts of Curcumin, Ginger, Clove and Amygdaline in Ehrlich Ascites Carcinoma-Challenging Mice.

Due to its systemic toxicity, traditional chemotherapy of tumors is being taken into consideration. Herbal therapy, containing phytochemical polyphenol derivatives such as Curcumin (Cur), Ginger (Gin), Cloves (Clov) and Amygdaline (Amyg), is one of the numerous complementary and alternative approaches as an anti-cancer therapy and holds great promise for cancer chemo-prevention with fewer side effects. The current study was designated to assess anti-tumoral immunity and anti-cancer and chemo-preventive effectiveness of herbal extracts of Cur, Ginger, Clov and Amyg in Ehrlich Ascites Carcinoma (EAC)-challenging mice. Chemo-preventive efficacy of herbal extracts of Cur, Gin, Clov and Amyg were analyzed in vivo by examination of the apoptosis rate of EAC tumor cells by flow cytometry. The total numbers of EAC cells, splenocytes counts and leucocytes count with their differentials relative % in peripheral blood (PB) of EACchallenging mice were investigated. EAC-challenging mice treated with herbal extracts of Cur, Gin, Clov and Amyg showed a marked decline in EAC tumor cell count and a noticeable increase in apoptosis rate of EAC tumor cells, a remarkable decrease in serum level of cancer antigen 125 (CA-125) with an obvious increase in the number of splenocytes comparing to that in EAC-challenging mice treated with PBS alone. Moreover, the data indicated an insignificant change in the total leucocytes count and their differentials relative % of eosinophil, neutrophils, monocytes and lymphocytes in EAC-challenging mice treated with Cur and Amyg, but these parameters were markedly increased in EAC-challenging mice injected with Gin and Clov compared to that in EAC-challenging mice treated with PBS alone. To conclude, the herbal extracts of Cur, Gin, Clov and Amyg may have anti-tumoral immunity and anti-cancer potency and potential to reduce the resistance to cancer conventional chemotherapy and exert cancer chemo-protective approaches with low adverse effects. Further research is necessary to determine the regimen's toxicity on various tissues and organs and to connect the diagnostic and therapeutic approaches used in the regimen's biomedical use.

Synergistic Antineoplastic and Immunomodulatory Effects of Hesperidin in Ehrlich Ascites Carcinoma Tumor Model Treated with Cisplatin

Synergistic Antineoplastic and Immunomodulatory Effects of Hesperidin in Ehrlich Ascites Carcinoma Tumor Model Treated with Cisplatin

Doxorubicin and folic acid-loaded zinc oxide nanoparticles-based combined anti-tumor and anti-inflammatory approach for enhanced anti-cancer therapy

BackgroundZinc oxide nanoparticles (ZnONPs) have impressively shown their efficacy in targeting and therapy of cancer. The present research was designated to investigate the potential of ZnONP nanocomposites as a cancer chemotherapeutic-based drug delivery system and to assess the anti-tumor and anti-inflammatory effectiveness of ZnONP nanocomposites combination with systemic chemotherapeutic drugs doxorubicin (DOX) and folic acid (FA) in Ehrlich ascites carcinoma (EAC) tumor cell line both in vitro and in vivo.MethodsAnti-tumor potential of ZnONP nanocomposites: ZnONPs, ZnONPs/FA, ZnONPs/DOX and ZnONPs/DOX/FA against EAC tumor cell line was evaluated in vitro by MTT assay. Anti-tumor and anti-inflammatory efficacy of ZnONP nanocomposites were analyzed in vivo by examination of the proliferation rate and apoptosis rate of EAC tumor cells by flow cytometry, splenocytes count, level of inflammatory markers interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), as well as liver and kidney function in EAC-challenged mice.ResultsIn vitro results showed that ZnONP nanocomposites showed a high anti-proliferative potency against EAC tumor cells. Furthermore, the in vivo study revealed that the treatment EAC-challenged mice with ZnONPs, ZnONPs/DOX, ZnONPs/FA and ZnONPs/DOX/FA hindered the proliferation rate of implanted EAC tumor cells through lowering their number and increasing their apoptosis rate. Moreover, the treatment of EAC-challenged mice with ZnONPs/DOX/FA markedly decreased the level of IL-6 and TNF-α and remarkably ameliorated the liver and kidney damages that were elevated by implantation of EAC tumor cells, restoring the liver and kidney functions to be close to the naïve mice control.ConclusionZnONP nanocomposites may be useful as a cancer chemotherapeutic-based drug delivery system. ZnONP nanocomposites: ZnONPs/DOX, ZnONPs/FA and ZnONPs/DOX/FA regimen may have anti-inflammatory approaches and a great potential to increase anti-tumor effect of conventional chemotherapy, overcoming resistance to cancer systemic chemotherapeutics and reducing their side effects, offering a promising regimen for cancer therapy.

Antitumor Activity of Selenium in Ehrlich Ascites Carcinoma Bearing Mice

The most common disease states of chronic liver illnesses include alcoholic liver disease (ALD), and viral hepatitis can progress to hepatocellular carcinoma (HCC). However, the role of selenium-associated tumor management angiogenesis in liver fibrosis and inflammation is yet unknown. As a result, in this current study, cytotoxicity of selenium ( Se) was evaluated against hepatocellular carcinoma cells ( HepG2) to determine IC50 ( in vitro study) and we established a mouse model of Ehrlich Ascites Carcinoma (EAC) to explore the role of selenium in the processing of tumor angiogenesis in liver injury and inflammation ( in vivo study). EAC cells was used to induce ascites tumor in albino mice and studied their consequence role on body weight gain and liver e. In EAC tumor-bearing mice, we discovered a substantial increase in body weight. Furthermore, mice with EAC tumors had higher levels of liver enzymes implicated in the etiology of liver inflammation, as well as biomarkers such as tumor necrosis factor α (TNF-), α fetoprotein (AFP), and caspase-3, Bcl2, and DNA damage.

Newly Modified Nanoformulation of Quercetin as Promising Chemotherapeutic Anticancer Agent

Previous studies have demonstrated the potential anticancer effect of quercetin (QUR). However, water insolubility and less bioavailability of QUR reduce its efficiency in cancer therapy. So, this study aims to develop a nanoformulation of quercetin (QURnp) and evaluate its anticancer effect against Ehrlich ascites carcinoma (EAC)-bearing mice compared with native QUR. QUR- loaded pluronic nanoparticles (QURnp) were prepared and characterized. To investigate the anticancer effect of QUR and QURnp, histopathological, ultrastructural, immunohistochemical, cell cycle analysis, western blot, and qRT-PCR studies were performed on EAC tumor cells, as well as antioxidant biomarkers. The results showed that QURnp destroyed tumor cells and significantly elevated antioxidant status with the reduction in MDA and NO levels. QURnp caused mitochondrial degeneration in tumor cells. Furthermore, QURnp completely reduced tumor growth by inhibiting the IL-6/STAT3 signaling pathway, inducing cell cycle arrest at the G1/S phase via overexpression of p27 and suppression of angiogenesis via downregulation in VEGF gene expression. Moreover, immunohistochemical studies indicated that QURnp showed significant inhibition of proliferation marker Ki-67 and anti-apoptotic marker Bcl-2. This study demonstrated that QURnp is a promising anticancer agent superior to native QUR.

In vitro and in vivo anticancer potential and molecular targets of the new colchicine analog IIIM-067

ObjectiveThe current study evaluated various new colchicine analogs for their anticancer activity and to study the primary mechanism of apoptosis and in vivo antitumor activity of the analogs with selective anticancer properties and minimal toxicity to normal cells. MethodsSulforhodamine B (SRB) assay was used to screen various colchicine analogs for their in vitro cytotoxicity. The effect of N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(pyrrolidine-1-yl)5,6,7,9-tetrahydrobenzo[a] heptalene-7-yl] acetamide (IIIM-067) on clonogenicity, apoptotic induction, and invasiveness of A549 cells was determined using a clonogenic assay, scratch assay, and staining with 4′,6-diamidino-2-phenylindole (DAPI) and annexin V/propidium iodide. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels were observed using fluorescence microscopy. Western blot analysis was used to quantify expression of proteins involved in apoptosis, cell cycle, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling. Pharmacokinetic and in vivo efficacy studies against Ehrlich ascites carcinoma (EAC) and Ehrlich solid tumor models were conducted using Swiss albino mice. ResultsIIIM-067 showed potent cytotoxicity and better selectivity than all other colchicine analogs screened in this study. The selective activity of IIIM-067 toward A549 cells was higher among other cancer cell lines, with a selectivity index (SI) value of 2.28. IIIM-067 demonstrated concentration- and time-dependent cytotoxicity against A549 cells with half-maximal inhibitory concentration values of 0.207, 0.150 and 0.106 μmol/L at 24, 48 and 72 h, respectively. It also had reduced toxicity to normal cells (SI > 1) than the parent compound colchicine (SI = 1). IIIM-067 reduced the clonogenic ability of A549 cells in a dose-dependent manner. IIIM-067 enhanced ROS production from 24.6% at 0.05 μmol/L to 82.1% at 0.4 μmol/L and substantially decreased the MMP (100% in control to 5.6% at 0.4 μmol/L). The annexin V-FITC assay demonstrated 78% apoptosis at 0.4 μmol/L. IIIM-067 significantly (P < 0.5) induced the expression of various intrinsic apoptotic pathway proteins, and it differentially regulated the PI3K/AKT/mTOR signaling pathway. Furthermore, IIIM-067 exhibited remarkable in vivo anticancer activity against the murine EAC model, with tumor growth inhibition (TGI) of 67.0% at a dose of 6 mg/kg (i.p.) and a reduced mortality compared to colchicine. IIIM-067 also effectively inhibited the tumor growth in the murine solid tumor model with TGI rates of 48.10%, 55.68% and 44.00% at doses of 5 mg/kg (i.p.), 6 mg/kg (i.p.) and 7 mg/kg (p.o.), respectively. ConclusionIIIM-067 exhibited significant anticancer activity with reduced toxicity both in vitro and in vivo and is a promising anticancer candidate. However, further studies are required in clinical settings to fully understand its potential.

Oroxylum indicum stem bark extract exerts antitumor potential against Ehrlich’s ascites carcinoma in Swiss albino mice

Introduction and Aim: Constant efforts are exerted to explore unique bioactive principles from natural sources that possess more effective and specific antineoplastic activities. In the present study, we aimed to evaluate the antitumor activity of stem bark extract of Oroxylum indicum in mice bearing Ehrlich ascites carcinoma (EAC). Materials and Methods: Ninety female Swiss albino mice were categorized into fifteen groups (n=6). The animals were inoculated with 1x106 EAC cells. Tumor control animals received sterile water once daily for 10 consecutive days. Positive control group was injected with Cisplatin (CP) (one dose – 3.5 mg/kg body weight). The treatment groups were administered with O. indicum (OI) stem bark ethanol extract once daily with 50mg/kg, 200mg/kg and 400mg/kg body weight for eleven consecutive days. The blood parameters and serum hepatic enzymes activity was determined. The percentage increase in weight, the median survival time, the increase in median life span was calculated. The cytotoxic effect of CP and OI extract was determined. Results: There was significant reduction in the white blood cells count in OI and CP treatment group compared to increased level in EAC control group. The RBC count and Hemoglobin level which was significantly decreased (p&lt;0.05) in the tumour mice, was enhanced in the drug treatment groups. The EAC control group showed significant increase in tumour cell count (p&lt;0.05) whereas, treatment of EAC tumor bearing mice with OI and CP significantly increased the non-viable tumor cell count (p&lt;0.05). Conclusion: OI stem bark ethanol extract reduced the toxic implications of Ehrlich ascites carcinoma, reverted the haematological and biochemical changes induced by tumour. These results call for additional research on isolating and identifying the responsible bioactive elements in order to clarify the underlying processes of the anticancer impact.

Biogenic polymer-encapsulated diosgenin nanoparticles: Biodistribution, pharmacokinetics, cellular internalization, and anticancer potential in breast cancer cells and tumor xenograft

Diosgenin (DGN) is a natural bioactive steroidal saponin from therapeutic herbs and it exhibits potential anticancer efficacy. Here, we report the preparation of poly lactide-co-glycolide (PLGA)-encapsulated diosgenin nanoparticles (PLGA-DGN NPs) and characterization of their physicochemical nature, and morphology as well as inspect their drug-loading capability, in vitro drug release, pharmacokinetics, bio-distribution, safety profile. The in vitro and in vivo antineoplastic activities of PLGA-DGN NPs were also examined against the MCF-7 breast cancer cell line and in the Ehrlich ascites carcinoma (EAC) tumor xenograft model, respectively. The results displayed an appropriate size (∼147 nm), spherical shape, and a narrow polydispersity index. The nanoparticles showed a high encapsulation efficacy (78%), loading capacity (8%), good colloidal stability, and an initial burst release at an acidic medium. The nanoparticles exhibited significant cytotoxic activity at their IC50 dose compared to diosgenin. PLGA-DGN NPs facilitated cellular internalization of DGN in human breast cancer MCF-7 cells and extended the blood circulation time showing an excellent pharmacokinetic profile. Bio-distribution study revealed that PLGA-DGN NPs could significantly enhance DGN accumulation in tumor tissue. The safety profile of the PLGA-DGN NPs was confirmed in histopathologic, hematologic, and immunologic parameters of Swiss albino mice. At the same time, an effective antiangiogenic, and antiproliferative potential of PLGA-DGN NPs were exhibited in mice tumor xenograft model by showing tumor regression and down-regulating CD31 and Ki-67 expression. Therefore, PLGA-DGN NPs could be utilized as a promising anticancer drug, opening up a new avenue for further research.

Antitumor immunity and therapeutic properties of marine seaweeds-derived extracts in the treatment of cancer

Marine seaweeds are important sources of drugs with several pharmacological characteristics. The present study aims to evaluate the antitumor and antitumor immunological potentials of the extracts from the brown alga Padinapavonica and the red alga Janiarubens, inhibiting the Egyptian marine coasts. Hep-G2 cell lines were used for assessment of the antitumor efficacy of Padinapavonica and Janiarubens extracts in vitro, while Ehrlich ascites carcinoma (EAC) cells were applied to gain more antitumor immunity and antitumor insights of P.pavonica and J.rubens extracts in vivo. In vitro antitumor potentials of P.pavonica and J.rubens extracts were analyzed against human liver cancer Hep-G2 cells by MTT and trypan blue exclusion assays. In vivo antitumor immunological potentials of P.pavonica and J.rubens extracts at low, high, and prophylactic doses were analyzed by blood counting and flow cytometry in mice challenged with Ehrlich ascites carcinoma (EAC) cells. In vitro results revealed that P.pavonica and J.rubens extracts caused significant decreases in the number and viability of Hep-G2 cells in a dose-dependent manner as compared to untreated Hep-G2 cells or Cisplatin®-treated Hep-G2 cells. In vivo findings showed that P.pavonica and J.rubens extracts at low, high, and prophylactic doses significantly reduced the number and viability of EAC tumor cells accompanied by increases in EAC apoptosis compared to naïve EAC mouse. Additionally, P.pavonica and J.rubens extracts at low and prophylactic doses remarkably increased both the total WBC count and the relative numbers of lymphocytes and decreased the relative numbers of neutrophils and monocytes. Flow cytometric analysis showed that P.pavonica and J.rubens extracts at the treatment and the prophylactic doses resulted in a significant increase in the phenotypic expressions of CD4+ T, CD8+ T, and CD335 cells compared to naïve EAC mouse. Overall, both extracts P.pavonica and J.rubens possess potential antitumor and antitumor immunological effects with less toxicity, opening new approaches for further studies of the chemical and biological mechanisms behind these effects.

Enhanced antitumor activity of combined methotrexate and histone deacetylase inhibitor valproic acid on mammary cancer in vitro and in vivo.

Histone deacetylase inhibitors (HDACIs) act as antiproliferative agents by promoting differentiation and inducing apoptosis. Valproic acid (VPA) is a HDACI that shows promising chemotherapeutic effect in a number of tumor cells. The present study aimed to investigate the inhibitory effect of VPA on the viability of mammary cancer cells and its enhancing effect with methotrexate (MTX) in vitro and in vivo. Treatment with VPA or MTX alone induced concentration-dependent cytotoxic effects in two breast cancer cell lines. Valproic acid increased significantly the cytotoxicity of MTX three times against MCF7. Valproic acid addition to MTX, however, did not produce any significant changes on MTX cytotoxicity against MDA-MB231. VPA (150 and 200mg/kg) significantly inhibited the growth of Ehrlich ascites carcinoma (EAC) and solid Ehrlich carcinoma (SEC) tumor mouse models and improved results were achieved for tumor inhibition when VPA was combined with MTX (1 and 2mg/kg) in vivo. The antitumor activity was not associated with a significant increase in toxicity or mice mortality rate. All these findings suggest that the combination of MTX and VPA may have clinical and (or) adjuvant therapeutic application in the treatment of mammary cancer.

Chemical Profiling and Evaluation of Antioxidant and Anticancer Potential of Tuber Crop Amorphophallus commutatus var. wayanadensis.

Cancer and cancer-related diseases are a global health concern in the present scenario. Functional food and nutraceuticals are considered as a boon towards cancer management. Amorphophallus commutatus var. wayanadensis (ACW) is an herbaceous plant used by the local communities of Wayanad, India, for food and primary healthcare. Various radical scavenging and reducing power assays were undertaken to evaluate the antioxidant activity of methanolic extract of ACW (MEAC). In vitro anticancer activity was evaluated against HT-29 cell line by MTT assay, morphological analysis, DNA fragmentation assay and cell cycle analysis. Caspase and COX-2 enzyme assays were conducted to examine the underlying mechanism. Studies on Ehrlich Ascites Carcinoma (EAC) transplanted mice models was carried out to evaluate the in-vivo antioxidant and anticancer potential of MEAC. The major bioactive nutraceutical compound present in MEAC was isolated by bioactivity-guided fractionation. MEAC showed significant in vitro antioxidant activity. Further, MEAC promoted cytotoxicity against HT-29 cells by activating caspase-3 dependent apoptotic pathway with a cell cycle arrest at the G1/S phase and subsequent down regulation of COX-2 pathway. The potential antitumor activity of MEAC was further confirmed in EAC tumor bearing mice models in which treatment with MEAC increased the levels of antioxidant enzymes, improved the hematological profile towards normal and also augmented the life span of tumor bearing mice. β-sitosterol isolated from ACW induces anticancer activity via caspase-dependent pathway. Our study confirmed the antioxidant and anticancer activities of ACW, which proposes the medicinal importance of this plant as a preventive and supportive therapy for arising tumors.

Immunomodulatory potential of the ethyl acetate fraction of Pinus roxburghii from the Himalayan region of India towards Ehrlich ascites carcinoma

Pinus roxburghii commonly known as “chir pine” belongs to the family Pinaceae and is one of the ornamental trees having tremendous medicinal values placed all over the temperate territory of the northern hemisphere including the Himalayas. There is a global interest in the scientific community to identify novel therapeutic agents that may fight against cancer. In the present study, ethyl acetate fractions (EAF) of green and fallen needles of Pinus roxburghii from the Himalayan region of Himachal Pradesh, India were investigated for immunostimulatory potential toward cancer reduction under both in vitro and in vivo conditions. The previous preliminary study is baselined for the novel idea of using ethyl acetate fractions of green and fallen needles of Pinus roxburghii to assess immunomodulation on Ehrlich ascites carcinoma (EAC) tumor model among six extracts and fractions. A 10 mg/kg body weight of EAF was injected intraperitoneally for 7 days for immunostimulation of mice prior to cancer induction and compared with standard immunostimulator levamisole. After 14 days of EAC inoculation, hematological, biochemical parameters and vital organs were analyzed. The in vitro data depicted that EAF of green and fallen needles of P. roxburghii possessed the highest immunoenhancing potential on human peripheral blood lymphocytes. Pre-treatment with EAF at 10 mg/kg of the body weight, enhanced the mean survival time to (% ILS=55) and (% ILS=58) respectively in percentage increased life span, whereas it was found to be (% ILS=78) for levamisole. Moreover, EAF of both needles indicated a reduction in tumor growth up to 70.3% while levamisole exhibited 85.4% compared to tumor control groups via immune boosting. Histological examinations revealed enhanced cell number and increased sizes of spleen and thymus indicating boosted immunological responses of EAFs. Hematological and biochemical parameters were recorded to be normal compared to tumor control. The study presented here proved that EAF of green and fallen needles of P. roxburghii have a novel, potential and rich source of immune-boosting phytochemicals for fighting tumor development. Therefore EAF of the needles may be used to develop novel alternative immune boosters which can fight against the development of various types of cancers.

In vivo toxicity and antitumor activity of newly green synthesized reduced graphene oxide/silver nanocomposites

A novel biosynthesis of dual reduced graphene oxide/silver nanocomposites (rGO/AgNC) using the crude metabolite of Escherichia coli D8 (MF06257) strain and sunlight is introduced in this work. Physicochemical analysis of these rGO/AgNC revealed that they are sheet-like structures having spherically shaped silver nanoparticles (AgNPs) with an average particle size of 8 to 17 nm, and their absorption peak ranged from 350 to 450 nm. The biosynthesized rGO/AgNC were characterized by UV–vis and FT-IR spectra, X-ray diffraction, Zeta potential and transmission electron microscopy. After the injection of these nanocomposites to mice, their uptake by the kidney and liver has been proven by the ultrastructural observation and estimation of the hepatic and renal silver content. These nanocomposites caused a moderate toxicity for both organs. Changes in the liver and kidney functions and histopathological effects had been observed. The rGO/AgNC revealed a remarkable antitumor effect. They showed a dose-dependent cytotoxic effect on Ehrlich ascites carcinoma (EAC) cells in vitro. Treatment of mice bearing EAC tumors intraperitoneally with 10 mg/kg rGO/AgNC showed an antiproliferative effect on EAC cells, reduced ascites volume, and maintained mice survival. The results indicate that this green synergy of silver nanoparticles with reduced graphene oxide may have a promising potential in cancer therapy.

Evaluation of anticarcinogenic and antioxidant properties of Eruca sativa extracts versus Ehrlich ascites carcinoma in mice

ObjectiveCancer is a major public health issue and characterized by wild cell growth and proliferative disorder. The antitumor and antioxidant role of Eruca sativa (ES) was investigated in a Ehrlich ascites carcinoma (EAC) tumor model in mice. MethodsTwenty-four hours after EAC intraperitoneal inoculation in mice, ES extracts were administered at doses of 250 mg/kg/body weight (BW) for 9 days. Half of the mice were sacrificed on the 10th day for estimation of hematological profiles, red blood cell count, hemoglobin content, packed cell volume, mean corpuscular volume and mean corpuscular hemoglobin. In addition, antioxidant parameters (superoxide dismutase, catalase, and glutathione peroxidase) were evaluated. The remaining mice were kept alive to assess the increase in life span. Aspartate aminotransferase, alanine transaminase, alkaline phosphatase, creatinine, and urea levels were assessed for ES antitumor effects. Results.Oral supplementation of ES seed and leaf extracts significantly reduced tumor parameters such as tumor volume and tumor weight with remarkable enhance in tumor inhibition ratio, vice versa, increased both survival and average BW of tumor-bearing mice. ES extracts significantly increased BW and extended the life span of tumor-bearing mice. Hematological profiles were restored to normal and modulated the abovementioned antioxidant parameters in ES-treated mice compared with EAC control. ConclusionThe current study noticeably demonstrates the antitumor activity of ES seed and leaf extracts significantly prolonged life span and normalized the hematological profiles and biochemical parameters compared with EAC mice.

Antitumor Effect of Bio-Fabricated Silver Nanoparticles Towards Ehrlich Ascites Carcinoma

The current study aimed to evaluate the in vitro and in vivo anticancer potential of the silver nanoparticles fabricated with butanol fraction of Pinus roxburghii needles (PNb-AgNPs). In vitro results revealed significant cytotoxicity of PNb-AgNPs towards Ehrlich Ascites Carcinoma (EAC) cells with an IC50 of 47.02 ± 1.11 μg/ml. Further, morphological changes, Reactive Oxygen Species (ROS) generation, mitochondrial depolarization, and DNA fragmentation elucidated EAC cell death by PNb-AgNPs exposure. The cell cycle analysis displayed an increase in the Sub-G1 population (52%), further confirmed by nuclear fragmentation in EAC cells after PNb-AgNPs treatment. The hemolytic investigation revealed the biocompatible nature of PNb-AgNPs. In vivo experiments were performed using the liquid Ehrlich Ascites Carcinoma tumor model, which clearly showed a reduction in tumor growth and body weight following PNb-AgNPs treatment in EAC-bearing mice as compared to untreated controls. Moreover, elevated hematological and biochemical parameters were found to restore to normal range in EAC-bearing mice treated with PNb-AgNPs. Overall, PNb-AgNPs effectively induced apoptotic cell death in EAC cells and exhibited remarkable in vivo antitumor potential.

Tuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice.

BackgroundTargeted multidrug-loaded delivery systems have emerged as an advanced strategy for cancer treatment. In this context, antibodies, hormones, and small peptides have been coupled to the surface of drug carriers, such as liposomes, polymeric and metallic nanoparticles loaded with drugs, as tumor-specific ligands. In the present study, we have grafted a natural macrophage stimulating peptide, tuftsin, on the surface of the liposomes (LPs) that were loaded with doxorubicin (DOX) and/or curcumin (CUR), by attaching to its C-terminus a palmitoyl residue (Thr-Lys-Pro-Arg-CO-NH-(CH2)2-NH-COC15H31, P.Tuft) to enable its grafting within the liposome’s bilayer.MethodsThe prepared drug-loaded liposomes (DOX LPs, CUR LPs, DOX-CUR LPs, P.Tuft-LPs, P.Tuft-DOX LPs, P.Tuft-CUR LPs, P.Tuft-DOX-CUR LPs) were thoroughly characterised in terms of particle size, drug content, encapsulation efficiency and structural properties using UV–visible spectroscopy, dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR). The anti-cancer activity and drug toxicity of the liposomal formulations were examined on Ehrlich ascites carcinoma (EAC) tumor-induced mice model.ResultsA significant reduction in the tumor weight and volume was observed upon treating the tumor-bearing mice with palmitoyl tuftsin-grafted dual drug-loaded liposomes (P.Tuft-DOX-CUR LPs), as compared to the single drug/peptide-loaded formulation (DOX LPs, CUR LPs, DOX-CUR LPs, P.Tuft- LPs, P.Tuft-DOX LPs, P.Tuft-CUR LPs). Western blot analysis revealed that the tumor inhibition was associated with p53-mediated apoptotic pathway. Further, the biochemical and histological analysis revealed that the various liposomal preparation used in this study were non-toxic to the animals at the specified dose (10mg/kg).ConclusionIn conclusion, we have developed a targeted liposomal formulation of P.Tuftsin-bearing liposomes co-encapsulated with effective anti-cancer drugs such as doxorubicin and curcumin. In experimental animals, tumor inhibition by P.Tuft-DOX-CUR LPs indicates the synergistic therapeutic effect of the peptide and the dual drug.

Echinochrome Exhibits Antitumor Activity against Ehrlich Ascites Carcinoma in Swiss Albino Mice

Background: Echinochrome (Ech) is a common pigment present in sea urchins, which has antioxidant, antimicrobial, antialgal, hypolipidemic and hypoglycemic activities.Purpose: The present investigation assessed the anticancer and antioxidant activities of Ech against the Ehrlich ascites carcinoma tumor model in mice.Methods: Forty female mice were divided into four groups (n = 10). All groups except the group I received EAC cells (5 × 106 cells/mouse i.p.). Group I, served as saline control (5 ml/kg 0.9% NaCl w/v p.o); group II served as EAC; groups III and IV received Ech (1 mg/kg body weight i.p.), and reference drug (5-Fu, 20 mg/kg body weight i.p.) respectively. Tumor markers, hematological parameters, liver functions, kidney functions and oxidative stress markers were analyzed in the present study.Results: A significant decrease (p < 0.05) were detected in the tumor volume, tumor cell counts, tumor cells viability, WBC count, MDA, urea, uric acid, AST, ALT, and ALP levels in Ech-treated mice. Furthermore, Ech-treated mice showed significant increases in RBCs count, Hb, Pt, GSH, CAT, and GST levels.Conclusion: The study results revealed that echinochrome suppresses tumor growth, decreases lipid peroxidation and improves the antioxidant status.

Synthesis, Characterization, and In Vivo Anti-Cancer Activity of New Metal Complexes Derived from Isatin-N(4)antipyrinethiosemicarbazone Ligand Against Ehrlich Ascites Carcinoma Cells

The current study aimed to synthesize new metal coordination complexes with potential biomedical applications. Metal complexes were prepared via the reaction of isatin-N(4)anti- pyrinethiosemicarbazone ligand 1 with Cu(II), Ni(II), Co(II), Zn(II), and Fe(III) ions. The obtained metal complexes 2–12 were characterized using elemental, spectral (1H-NMR, EPR, Mass, IR, UV-Vis) and thermal (TGA) techniques, as well as magnetic moment and molar conductance measurements. In addition, their geometries were studied using EPR and UV–Vis spectroscopy. To evaluate the in vivo anti-cancer activities of these complexes, the ligand 1 and its metal complexes 2, 7 and 9 were tested against solid tumors. The solid tumors were induced by subcutaneous (SC) injection of Ehrlich ascites carcinoma (EAC) cells in mice. The impact of the selected complexes on the reduction of tumor volume was determined. Also, the expression levels of vascular endothelial growth factor (VEGF) and cysteine aspartyl-specific protease-7 (caspase-7) in tumor and liver tissues of mice bearing EAC tumor were determined. Moreover, their effects on alanine transaminase (ALT), aspartate transaminase (AST), albumin, and glucose levels were measured. The results revealed that the tested compounds, especially complex 9, reduced tumor volume, inhibited the expression of VEGF, and induced the expression of caspase-7. Additionally, they restored the levels of ALT, AST, albumin, and glucose close to their normal levels. Taken together, our newly synthesized metal complexes are promising anti-cancer agents against solid tumors induced by EAC cells as supported by the inhibition of VEGF and induction of caspase-7.

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.

Antitumor activity of saponin isolated from the sea cucumber, holothuria arenicola against ehrlich ascites carcinoma cells in swiss albino mice

The present investigation attempted study the potential use of the Holothuria arenicola saponin (HaS) against Ehrlich Ascites Carcinoma (EAC) tumor model in female Swiss albino mice. The HPLC studies of the extracted saponin showed the peak at retention time 5.19 min. was is matched with the standard saponin with total amount 34.87%. Significant improvements were detected in the tumor markers, complete blood count, antioxidant system, liver function and kidney function of HaS-treated mice. The present study demonstrated that HaS is a potent natural product that has promising antineoplastic efficacy.