Bismuth Nanoparticles Increase Effectiveness of Proton Therapy of Ehrlich Carcinoma.

We studied the antitumor activity of the combined use of local proton irradiation in two modes (10 and 31 Gy) with preliminary intra-tumoral injection of two types of bismuth nanoparticles differing in surface coating: coated with the amphiphilic molecule Pluronic-F127 or Silane-PEG (5 kDa)-COOH polymer. Nanoparticles were used in doses of 0.75 and 1.5 mg/mouse. In two independent series on experimental tumor model (solid Ehrlich carcinoma), bismuth nanoparticles of both modifications injected directly into the tumor enhanced the antitumor effects of proton therapy. Moreover, the radiosensitizing effect of bismuth nanoparticles administered via this route increased with the increasing the doses of nanoparticles and the doses of radiation exposure. In our opinion, these promising data obtained for the first time extend the possibilities of treating malignant neoplasms.

Trichinella spiralis Larval Extract as a Biological Anti-Tumor Therapy in a Murine Model of Ehrlich Solid Carcinoma.

Trichinella spiralis (T. spiralis) is an immunomodulating parasite that can adversely affect tumor growth and extend host lifespan. The aim of this study was to elucidate the mechanisms by which T. spiralis larval antigens achieve this effect using Ehrlich solid carcinoma (ESC) murine model. Assessment was done by histopathological and immunohistochemical analysis of caspase-3, TNF-α, Ki-67 and CD31. Additionally, Bcl2 and Bcl2-associated protein X (Bax) relative gene expression was assessed by molecular analysis for studying the effect of T. spiralis crude larval extract (CLE) antigen on tumor necrosis, apoptosis, cell proliferation and angiogenesis. We found that both T. spiralis infection and CLE caused a decrease in the areas of necrosis in ESC. Moreover, they led to increased apoptosis through activation of caspase-3, up-regulation of pro-apoptotic gene, Bax and down-regulation of anti-apoptotic gene, Bcl2. Also, T. spiralis infection and CLE diminished ESC proliferation, as evidenced by decreasing Ki-67. T. spiralis infection and CLE were able to suppress the development of ESC by inhibiting tumor proliferation, inducing apoptosis and decreasing tumor necrosis, with subsequent decrease in tumor metastasis. T. spiralis CLE antigen may be considered as a promising complementary immunotherapeutic agent in the treatment of cancer.

Smart chitosan nanogel for targeted doxorubicin delivery, ensuring precise release, and minimizing side effects in Ehrlich ascites carcinoma-bearing mice.

In recent decades, bio-polymeric nanogels have become a forefront in medical research as innovative in-vivo drug carriers. This study introduces a pH-sensitive chitosan nanoparticles/P(N-Isopropylacrylamide-co-Acrylic acid) nanogel (CSNPs/P(NIPAm-co-AAc)), making significant advancements. The nanogel effectively encapsulated doxorubicin hydrochloride (Dx. HCl), a model drug, within its compartments through electrostatic binding. Comparing nano chitosan (CSNPs) before and after integrating copolymerized P(NIPAm-co-AAc), highlighting an improved and adaptable nanogel structure with responsive behaviors. The intraperitoneal delivery of Dx-loaded nanogel (Dx@N.gel) to Ehrlich ascites carcinoma (Eh)-bearing mice at doses equivalent to 1.5 and 3 mg/kg of Dx per day for 14 days exhibited superiority over the administration of free Dx. Dx@N.gel demonstrated heightened anticancer activity, significantly improving mean survival rates in Eh mice. The nanogel's multifaceted defense mechanism mitigated oxidative stress, inhibited lipid peroxidation, and curbed nitric oxide formation induced by free Dx. It effectively countered hepatic DNA deterioration, normalized elevated liver and cardiac enzyme levels, and ameliorated renal complications. This pH-responsive CSNPs/P(NIPAm-co-AAc) nanogel loaded with Dx represents a paradigm shift in antitumor drug delivery. Its efficacy and ability to minimize side effects, contrasting sharply with those of free Dx, offer a promising future where potent cancer therapies seamlessly align with patient well-being.

Alocasia macrorrhiza rhizome lectin inhibits growth of pathogenic bacteria and human lung cancer cell in vitro and Ehrlich ascites carcinoma cell in vivo in mice.

Cancer and antibiotic resistance represent significant global challenges, affecting public health and healthcare systems worldwide. Lectin, a carbohydrate-binding protein, displays various biological properties, including antimicrobial and anticancer activities. This study focused on anticancer and antibacterial properties of Alocasia macrorrhiza lectin (AML). AML, with a molecular weight of 11.0 ± 1.0 kDa was purified using Ion-exchange chromatography, and the homotetrameric form was detected by gel-filtration chromatography. It agglutinates mouse erythrocytes, that was inhibited by 4-Nitrophenyl-α-d-mannopyranoside. Maximum hemagglutination activity was observed below 60 °C and within a pH range from 8 to 11. Additionally, it exhibited moderate toxicity against brine shrimp nauplii with LD50 values of 321 µg/ml and showed antibacterial activity against Escherichia coli and Shigella dysenteriae. In vitro experiments demonstrated that AML suppressed the proliferation of mice Ehrlich ascites carcinoma (EAC) cells by 35 % and human lung cancer (A549) cells by 40 % at 512 µg/ml concentration. In vivo experiments involved intraperitoneal injection of AML in EAC-bearing mice for five consecutive days at doses of 2.5 and 5.0 mg/kg/day, and the results indicated that AML inhibited EAC cell growth by 37 % and 54 %, respectively. Finally, it can be concluded that AML can be used for further anticancer and antibacterial studies.

Dioon rzedowskii: An antioxidant, antibacterial and anticancer plant extract with multi-faceted effects on cell growth and molecular signaling.

This study investigated the antioxidant, anticancer, antibacterial properties of Dioon rzedowskii extract, which had not been previously explored. We aimed to determine the extract's effect on liver and breast cancer cell lines and on solid Ehrlich carcinoma (SEC) mouse model to investigate the underlying molecular mechanisms. Three female albino mice groups were established: a tumor control group, a group treated with 100 mg/kg of the extract (D100), and a group treated with 200 mg/kg of the extract (D200) for 16 days after tumor development. Results showed that the D. rzedowskii extract inhibited cell growth in both MCF-7 and HepG2 cells in a concentration-dependent manner. This was achieved by suppressing the cell proliferation and inducing apoptosis. The extract also improved liver, heart, and kidney functions compared to the tumor control. Furthermore, oral administration of the extract reduced tumor volume and alleviated oxidative stress in tumor tissue. The anticancer effects were associated with overexpression of p53 and Bax and downregulation of cyclin D1 expression, which was attributed to decreased phosphorylated MAPK kinases. Additionally, D. rzedowskii exhibited antibacterial activity against K. pneumoniae isolated from cancer patients. The extract inhibited bacterial growth and reduced the membrane integrity. The study suggests that D. rzedowskii has promising potential as an adjunctive therapy for cancer treatment. Further investigations are needed to explore its combined anticancer efficacy. These results emphasize the value of natural products in developing compounds with potential anticancer activity and support a paradigm shift in cancer management to improve patients' quality of life.

Ehrlich ascites carcinoma provokes renal toxicity and DNA injury in mice: Therapeutic impact of chitosan and maitake nanoparticles.

In this study, the impact of chitosan (CS) and maitake (GF) nanoparticles towards the renal toxicity induced by Ehrlich ascites carcinoma (EAC) in vivo model was conducted. Besides benchmark negative control group, EAC model was constructed by intraperitoneal injection (i.p.) of 2.5 × 106 cells. Alongside positive control, two groups of EAC-bearing mice received 100 mg/kg of CS and GF nanoparticles/body weight daily for 14 days. The kidney function was conducted by measuring urea, creatinine, ions, (anti)/oxidative parameters and DNA damage. Also, measuring immunoreactivity of P53, proliferating cell nuclear antigen (PCNA), and B-cell lymphoma 2 (Bcl-2) and apoptosis protein. The outcomes illustrated notable kidney toxicity, which indicated by elevations in urea, creatinine, oxidative stress, DNA damage and induction of apoptosis. These events were supported by the drastic alteration in kidney structure through histological examination. Administration of CS and GF nanoparticles was able to enhance the antioxidant power, which further reduced oxidative damage, DNA injury, and apoptosis. These results indicated the protective and therapeutic role of biogenic chitosan and maitake nanoparticles against nephrotoxicity.

Antitumor Activity of a Lectin Purified from Punica granatum Pulps against Ehrlich Ascites Carcinoma (EAC) Cells.

BACKGROUND: Lectins are carbohydrate-binding proteins with various pharmacological activities, such as antimicrobial, antidiabetic, antioxidant, and anticancer. Punica granatum fruit extract has traditional uses, however, the anti-cancer activity of purified lectin isolated from P. granatum pulp is yet to be reported. OBJECTIVE: The goals of this study are purification, characterization of the lectin from P. granatum, and examination of the purified lectin's anticancer potential. METHODS: Diethylaminoethyl (DEAE) ion-exchange chromatography was used to purify the lectin, and SDSPAGE was used to check the purity and homogeneity of the lectin. Spectrometric and chemical analysis were used to characterize the lectin. The anticancer activity of the lectin was examined using in vivo and in vitro functional assays. RESULTS: A lectin, designated as PgL of 28.0 ± 1.0 kDa molecular mass, was isolated and purified from the pulps of P. granatum and the lectin contains 40% sugar. Also, it is a bivalent ion-dependent lectin and lost its 75% activity in the presence of urea (8M). The lectin agglutinated blood cells of humans and rats, and sugar molecules such as 4-nitrophenyl-α-D-manopyranoside and 2- nitrophenyl -ß- D-glucopyranoside inhibited PgL's hemagglutination activity. At pH ranges of 6.0-8.0 and temperature ranges of 30°C -80°C, PgL exhibited the highest agglutination activity. In vitro MTT assay showed that PgL inhibited Ehrlich ascites carcinoma (EAC) cell growth in a dose-dependent manner. PgL exhibited 39 % and 58.52 % growth inhibition of EAC cells in the mice model at 1.5 and 3.0 mg/kg/day (i.p.), respectively. In addition, PgL significantly increased the survival time (32.0 % and 49.3 %) of EAC-bearing mice at 1.5 and 3.0 mg/kg/day doses (i.p.), respectively, in comparison to untreated EAC-bearing animals (p < 0.01). Also, PgL reduced the tumor weight of EAC-bearing mice (66.6 versus 39.13%; p < 0.01) at the dose of 3.0 mg/kg/day treatment. Furthermore, supplementation of PgL restored the haematological parameters toward normal levels deteriorated in EAC-bearing animals by the toxicity of EAC cells. CONCLUSION: The results indicated that the purified lectin has anticancer activity and has the potential to be developed as an effective chemotherapy agent.

Euphorbia grantii Oliv. standardized extract and its fraction ameliorate doxorubicin-induced cardiomyopathy in Ehrlich carcinoma bearing mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia plants have long been used as traditional medicine in China, Europe, America, Turkey, India, Africa, Iran, and Pakistan because of its high medicinal value and health advantages especially as a remedy for several types of cancer. AIM OF THE STUDY: Doxorubicin (DOX) is one of the most frequently prescribed drugs in cancer chemotherapy, with dose-limiting cardiotoxicity. The development of medicinal approaches to attenuate drug's toxicity represents an area of great concern in cancer research. Because research on this topic is still disputed and limited, we aim to investigate the potential of supplementation with Euphorbia grantii Oliv. on DOX-induced cardiomyopathy in Ehrlich carcinoma bearing mice. MATERIALS AND METHODS: The high-performance thin layer chromatography (HPTLC) analysis of total methanolic extract (TE), and its bioactive dichloromethane fraction (DCMF) was applied for the determination of friedelin. Male BALB/c mice were used to keep the Ehrlich ascites tumor cells. The experiment was performed for a 2-weeks period. RESULTS: A good linearity relationship was found to be with correlation coefficient (r2) value of 0.9924 for the isolated friedelin. Limit of detection (LOD) and limit of quantitation (LOQ) was found to be 0.00179, and 0.000537 ng/band respectively for friedelin. The amount of friedelin in the TE and DCMF were determined by using calibration curve of standard as 106.32 ± 5.69 µg, and 159.2 ± 4.24 µg friedelin/mg extract, respectively. DOX-induced cardiomyopathy by decreasing the ejection fraction (EF) compared to the Ehrlich and negative control groups. It resulted in a decrease in the EF by 30 and 39% compared to the other groups. High and low doses of the TE and DCMF did not result in significantly different ejection fractions compared to the Ehrlich group. Co-administration of DCMF with DOX ameliorated the alteration in the serum CKMB and LDH levels. As revealed from histopathological study, DOX impairs viability of cardiac myocytes and DCMF could effectively and extensively counteract this action of DOX and potentially protect the heart from severe toxicity of DOX. CONCLUSIONS: Finally, our results indicated that Euphorbia grantii Oliv. would be the best option to reduce DOX adverse effects.

Molecular Docking and In Vivo Biological Studies of Sodium Salt of 3-(4-Methyl-2-oxo-2-H-quinoline-7-yloxy)-3-phenylacrylic Acid As Anticancer Agent.

Quinoline derivatives possess several therapeutic properties. Aim: studying the anticancer effect of 3-(4-methyl-2-oxo-2-H-quinoline-7-yloxy)-3-phenylacrylic acid's sodium solution on the Ehrlich ascites carcinoma (EAC). Median lethal dose (LD50) and dose response curve was determined for sodium salt solution of 3-(4-methyl-2-oxo-2-H-quinoline-7-yloxy)-3-phenylacrylic acid, then diving a group of one hundred Swiss albino mice, which are all females, into five groups: group 1: (negative control) where intraperitoneally injected with saline into mice for 10 successive days; group 2 (positive control), also namely (EAC-bearing group): where the EAC cells were intraperitoneally injected into mice (2.5 × 106 cells/mouse) only one time on the first day; group 3 which is defined as the (therapeutic group) where the Na+ salt of the synthetic compound was injected into the peritoneum of the mice (2.5 mg/kg) the very first day after the injection of the EAC, then the compound was injected every two days for a period of 10 days; group 4 which is the (preventive group) where the sodium salt of the synthetic compound (2.5 mg/kg) was injected in the peritoneum of the mice the day before the injection of the EAC, then the compound was successively injected every day for a period of ten days; and group 5 which is the (drug group) in which mice were repeatedly injected) in their peritoneum with the sodium salt of the synthetic compound (2.5 mg/kg on a daily basis over a period of ten days. On the eleventh day of the trial, EAC cells were harvested from each mouse in a heparinized saline, in addition to blood samples, liver and kidney tissues which are also collected. Molecular docking showed that compound's sodium salt was docked into (PDB: 2R7G) and (PDB: 2R3I), which are the retinoblastoma protein receptor and the cyclin D-1 receptor respectively. Compared to those in the positive control group, mice in both the therapeutic and preventive groups, has shown a significant decrease in MDA, cyclin D-1 levels in the tissues of both liver and kidney tissues, in addition to the serum ALT, AST, CK-MB, and LDH activities, and the serum urea and creatinine concentration. However, mice in the formerly mentioned groups, both therapeutic and preventive groups, have shown an increase in the serum albumin, total protein, retinoblastoma protein in both liver and kidney tissues as well as the total antioxidant capacity, when compared to mice in the positive control group. It is worth mentioning that histopathological findings have confirmed that. Sodium salt of 3-(4-methyl-2-oxo-2H-quinoline-7-yloxy)-3-phenylacrylic acid showed potential in vivo anticancer and antioxidant effects against Ehrlich ascites carcinoma cells; (EAC cells).

Evaluation of antioxidant, anti-inflammatory, anticancer activities and molecular docking of Moringa oleifera seed oil extract against experimental model of Ehrlich ascites carcinoma in Swiss female albino mice.

The current research intended to evaluate the antitumor properties of Moringa oleifera oil extract (MOE). Fifty-six female Swiss albino mice were employed in this study. Animals were assigned into four groups: control (C) group, moringa oil extract (MOE) group administered (500 mg/kg b. wt) MOE daily via gavage, Ehrlich ascites carcinoma (EAC) group and EAC group administered daily with (500 mg/kg b.wt) MOE for two weeks (EAC/MOE). The results showed that MOE significantly ameliorated the EAC increase in body weight and reduced the EAC cell viability. In addition, they upgraded the levels of hepatic and renal functions, inflammatory cytokines, oxidative stress markers and EAC-induced hepatic and renal histopathological changes. Treatment of EAC with MOE induced antitumor, anti-inflammatory and antioxidant effects and normalized most of the tested parameters besides the histopathological alterations in both renal and hepatic tissues. HPLC for the MOE identified Cinnamic acid, Ellagic acid, Quercetin, Gallic acid, Vanillin and Hesperidin as major compounds. The molecular docking study highlighted the virtual binding of the identified compounds inside the GSH and SOD proteins, especially for Quercetin which exhibited promising binding affinity with good interactive binding mode with the key amino acids. These results demonstrate that the antitumor constituents of MOE against EAC induced oxidative stress and inflammation by preventing oxidative damage and controlling EAC increase.

Growth Induction of Solid Ehrlich Ascitic Carcinoma in Mice after Proton Irradiation of Tumor Cells Ex Vivo.

This study presents data on the growth rate and frequency of induction of the solid form of Ehrlich's ascites carcinoma (EAC) in mice in the short and long term after inoculation of ascitic cells irradiated ex vivo with a proton beam in the dose range of 30-150 Gy. It was shown that the growth rate of solid tumors after inoculation of irradiated cells ex vivo coincided with the growth of tumors in the control group. The frequency of tumor induction in mice after inoculation of EAC cells irradiated at a dose of 30 Gy was 80%, 60 Gy-60%, 90 Gy-25%, and 120 Gy-10%; at irradiation at a dose of 150 Gy, no tumors appeared during the entire observation period. Thus, we determined the dose of proton radiation required to eliminate tumor cells and/or signaling factors that can lead to the induction of tumor growth of EAC in mice.

Suppression of VEGF and inflammatory cytokines, modulation of Annexin A1 and organ functions by galloylquinic acids in breast cancer model.

The ongoing development of novel drugs for breast cancer aims to improve therapeutic outcomes, reduce toxicities, and mitigate resistance to chemotherapeutic agents. Doxorubicin (Dox) is known for its significant side effects caused by non-specific cytotoxicity. In this study, we investigated the antitumor activity of galloylquinic acids (BF) and the beneficial role of their combination with Dox in an Ehrlich ascites carcinoma (EAC)-bearing mouse model, as well as their cytotoxic effect on MCF-7 cells. The EAC-mice were randomized into five experimental groups: normal saline, Dox (2 mg/kg, i.p), BF (150 mg/kg, orally), Dox and BF combined mixture, and a control group. Mice were subjected to a 14-day treatment regimen. Results showed that BF compounds exerted chemopreventive effects in EAC mice group by increasing mean survival time, decreasing tumor volume, inhibiting ascites tumor cell count, modulating body weight changes, and preventing multi-organ histopathological alterations. BF suppressed the increased levels of inflammatory mediators (IL-6 and TNF-α) and the angiogenic marker VEGF in the ascitic fluid. In addition, BF and their combination with Dox exhibited significant cytotoxic activity on MCF-7 cells by inhibiting cell viability and modulating Annexin A1 level. Moreover, BF treatments could revert oxidative stress, restore liver and kidney functions, and normalize blood cell counts.

Anticancer potential of Nymphaea nouchali Brum flowers against Ehrlich ascites carcinoma cell lines.

Background: Nymphaea nouchali Brum is exotic and medicinal plant in India. Aim of the Study: The main of this study is to evaluate the anticancer properties of Nymphaea nouchali Brum flowers against Ehrlich ascites carcinoma (EAC)-induced Swiss albino mice. Materials and Methods: The anticancer properties of Nymphaea nouchali Brum dry and fresh methanol extracts was investigated using EAC in Swiss albino mice. After inoculation of EAC cells into mice, treatment with NNDM flower extract (200 and 400 mg/kg) and standard drug 5-Fluorouracil (20 mg/kg) was continued for 9 days. The evaluation of the effect of drug response was made by the study of tumor growth response including increase in lifespan, the study of hematological parameters, biochemical estimations, and antioxidant assay of liver tissue compared to EAC control. The viability of cancer cell lines (such as HeLa, MCF-7, and MDA-MB 231 cells) was evaluated by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Results: Therefore, from the results of the present study, it can be concluded that NNDM exhibited significant antitumor activity against EAC in Swiss albino mice. The effect of NNDM on viability of cancer cell lines (such as HeLa, MCF-7, and MDA-MB 231 cells) was evaluated by MTT assay, apoptosis in HeLa cell lines was evaluated by DNA laddering assay, HeLa cells treated with NNDM exhibited a characteristic "ladder" pattern after separation of the fragments by agarose gel electrophoresis and subsequent visualization, by ethidium bromide staining. NNDM exhibited a significant effect on cell viability. Conclusions: Based on results, it was concluded that NNDM exhibited cytotoxic effect on cancer cells and, from DNA laddering assay, it can be concluded that NNDM-induced apoptosis in EAC cells.

The Effect of Iron Oxide Nanoparticles of Acalypha wilkesiana Ethyl Acetate Extract on Ehrlich Ascites Carcinoma Cells.

BACKGROUND: Nanoparticles' precise targeting properties are becoming increasingly important in treating cancer and starting to outweigh cancer therapies. METHODS: The in vivo anticancer activity of ethyl acetate iron oxide nanoparticles (NPS EAE) of Acalypha wilkesiana Müll. Mosaica was tested using Ehrlich ascites carcinoma cells (EAC). RESULTS: The value of the median lethal dose LD50 limit was found to be 3000 mg/kg. The value count of EAC cells was significantly decreased to 150 ± 2.01 (106) and 275 ± 2.01 (106) cells for each preventive and therapeutic group related to the positive group (525 ± 4.3 (106) cell. Moreover, the results of biological markers decrease in alanine amino transferase activity (ALT), aspartate amino transferase activity (AST), creatinine (CREAT), UREA, albumin, globulin, and total protein level according to the confident group by restoring the abnormal dissimilarity in the biomedical parameters to normal values. Ethyl acetate nano particles induced apoptosis in hepatic and kidney cells. This was designated by increasing the apoptosis regulator Bcl-2 associated X (BAX) level and significantly reducing antiapoptotic assay B-cell lymphoma 2 (Bcl-2) level as an antiapoptotic marker. In the apoptotic marker BAX, there was a significant rise in therapeutic activity with a change of 273.87% and a significant increase in the preventive group with a change of 144.69% according to the positive group. However, in the antiapoptotic marker, Bcl-2 highly decreases in the therapeutic group and preventive group with changes -83.20% and -87.82% according to the positive group, which has a highly significant increase with a change of 5855%. CONCLUSION: Histopathology tests showed anticancer activity against (EAC) in both the preventive group and therapeutic group, especially in the preventive group in kidney organs showed no pathology with normal glomeruli and normal tubules, it also showed in liver foci of lobular inflammation with mild development of a portal tract accompanied by inflammation, but in the therapeutic group showed less activity than the preventive group as in the kidney many tubules displayed appearances of slight tubular injury with mild acute tubular injury and in the liver, the therapeutic group becomes a more effective representation in normal liver architecture, with no detected lobular or portal inflammation or confluent necrosis. So the preventive group was considered as protecting agent for the kidney organ. However, the therapeutic group is supposed to be the treatment agent for the liver organ. This is due to the fact that it has a defensive effect rather than a curative effect. There is a possibility that it is a favorable anticancer agent. Green synthesis of Fe3O4- NPS was successfully done using plant extract acting as a reducing, stabilizing, and capping agent.

Impact of Synthesized Indoloquinoline Analog to Isolates from Cryptolepis sanguinolenta on Tumor Growth Inhibition and Hepatotoxicity in Ehrlich Solid Tumor-Bearing Female Mice.

The study evaluated the antitumor efficacy of APAN, "synthesized indoloquinoline analog derived from the parent neocryptolepine isolated from the roots of Cryptolepis sanguinolenta", versus the chemotherapeutic drug etoposide (ETO) in Ehrlich solid tumor (EST)-bearing female mice as well as its protective effect against etoposide-triggered hepatic disorders. APAN showed an ameliorative activity against Ehrlich solid tumor and hepatic toxicity, and the greatest improvement was found in the combined treatment of APAN with ETO. The results indicated that EST altered the levels of tumor markers (AFP, CEA, and anti-dsDNA) and liver biomarker function (ALT, AST, ALP, ALB, and T. protein). Furthermore, EST elevated CD68 and anti-survivin proteins immuno-expressions in the solid tumor and liver tissue. Molecular docking studies were demonstrated to investigate their affinity for both TNF-α and topoisomerase II as target proteins, as etoposide is based on the inhibition of topoisomerase II, and TNF-α is quite highly expressed in the solid tumor and liver tissues of EST-bearing animals, which prompted the authors' interest to explore APAN affinity to its binding site. Treatment of mice bearing EST with APAN and ETO nearly regularized serum levels of the altered parameters and ameliorated the impact of EST on the tissue structure of the liver better than that by treatment with each of them separately.

Suppression of tumor growth and apoptosis induction by pomegranate seed nano-emulsion in mice bearing solid Ehrlich carcinoma cells.

Despite the high antioxidant and penetration ability of pomegranate seed oil (PSO), the in vivo antitumor activity of PSO nano-emulsion has not been well investigated. Therefore, this study was undertaken to estimate the antitumor activity and safety of PSO nano-emulsion in mice bearing Ehrlich solid carcinoma cells. For tumor inoculation, about 2 × 106 viable Ehrlich tumor cells (200 µl) were implanted intramuscularly in the left thigh of hind leg. Once a solid tumor appears on the 10th day of transplantation; the mice were randomly divided into five groups (5 animals/group). Characterization of the PSO nano-emulsion using a Zeta sizer Malvern instrument and transmission electron microscope (TEM) revealed that the PSO nano-droplets were well dispersed with an average particle size of 8.95 nm and a spherical shape. Treatment with PSO nano-emulsions caused a significant reduction in the tumor size and weight, in a dose dependent manner, compared to tumor control group. Marked dose dependent elevations in the DNA damage level together with significant increases in the tumor suppressor p53, Bax and Caspase genes and reductions in the anti-apoptotic Bcl2 gene were also observed in the tumor tissue of mice given PSO nano-emulsions. Histological examination also revealed apoptosis and necrosis of tumor cells and tumor infiltration with inflammatory cells after PSO nano-emulsion treatment. However, high DNA damage was noticed in the liver and kidney tissues of mice given the highest dose of PSO nano-emulsion (400 mg/kg). Therefore, we concluded that PSO nano-emulsion exhibited a potent antitumor activity through induction of DNA breaks that triggers apoptosis of tumor cells but the highest dose caused genotoxicity to liver and kidney tissues, thus it is recommended to use doses lower than 400 mg/kg of PSO nano-emulsion as an alternative drugs for chemotherapy.

Immunomodulatory, apoptotic and anti-proliferative potentials of sildenafil in Ehrlich ascites carcinoma murine model: In vivo and in silico insights.

Sildenafil is a potent phosphodiesterase-5 (PDE5) inhibitor that effectively inhibits cGMP and increases the strength of nitric oxide. PDE5 was overexpressed in several carcinomas, including breast cancer, which inhibited tumor growth and cell division. The current research aims to investigate the in vivo sildenafil's immunomodulatory and antineoplastic potentials against Ehrlich Ascites Carcinoma. This study looked at the effects of sildenafil mono-treatment and co-treatment with cisplatin; tumor cell count, viability and the inhibition rate were determined. Apoptosis, cell cycle distribution, alterations in tumor cells and splenocytes proliferation, changes in splenocytes immunophenotyping using flowcytometry, plasma levels of malondialdehyde (MDA), reduced glutathione (GSH), interferone (IFN)-γ, granzyme B, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and hematological alterations were detected. Additionally, docking study was conducted to get further insights on how Sildenafil exerts its activity. Sildenafil mono-treatment and co-treatment with cisplatin markedly reduced tumor cell count, viability, growth rate and proliferative capability accompanied by apoptosis enhancement and G0/G1 and sub G1 cells cycle arrest. Fortunately, sildenafil evoked efficient cellular immune response by increasing plasma levels of granzyme B and IFN-γ, proportion of splenic T cytotoxic (CD3+CD8+) and T helper (CD3+CD4+), accompanied by decrease in the proportion of splenic regulatory T cells. . Moreover, in silico data suggest LcK and MAPKs as the potential targets of sildenafil. Furthermore, sildenafil rebalanced the oxidant-antioxidant status by decreasing MDA and increasing GSH plasma levels. Sildenafil successfully retrieved various hematological values besides renal and hepatic functions in EAC-bearing animals. In conclusion, our results suggest that sildenafil could be potential safe anti-tumor agent with immuno-modulatory properties against Ehrlich ascites carcinoma.

Investigation of the effect of rhamnetin on mice injected with solid and ehrlich ascites tumor.

Rhamnetin is a flavonoid which contained in especially clove, such as apple, tea, and onion plant. Rhamnetin has been used in cancer research due to its antitumor and antioxidant properties. In this study, effects of rhamnetin administration at different doses on ascites and solid tumors were investigated in Balb/C mice bearing EAT model that originating from rat breast adenocarcinoma. Experimental procedure: Overall, 92 Balb-c mice were used in this study. EAT cells (1 × 106 cells) that harvested from stock animals were injected to all rats via intraperitoneal and subcutaneous route. Rhamnetin (100 µg/kg-200 µg/kg) were given intraperitoneally and subcutaneously during 10 and 15 days to the animals bearing ascites tumor and solid tumor, respectively. Throughout experiments, weight changes were recorded in all groups. The maximum weight increase was observed in the control group among all groups (ascites and solid tumor groups). In the treatment groups, the least weight increase were determined in 200-µg/kg rhamnetin applied. The lowest increase in tumor volume was observed in the group that received 200-µg/kg rhamnetin (2.84) when compared to tumor control group (3.67). Result and conclusion: We determined that the number of live and dead cells in the treatment groups administered with the mean rhamnetin dose (2.5 µg/ml) was found in the count made in the EAT cell line after the incubation periods. We observed that rhamnetin plays an important role against cancer formation. We have obtained important results in our study, but detailed studies on the relationship between rhamnetin and cancer are needed.

Targeting apoptosis in MCF-7 and Ehrlich ascites carcinoma cells by saponifiable fractions from green and black Vitis vinifera seed oil.

Grape seed (GS) oil is one of the potential functional foods. For the first time, we evaluated the therapeutic effects of GS oil saponifiable (Sap)-fraction from black (BSap) and green (GSap) grapes on MCF-7 cells and Ehrlich ascites carcinoma (EAC) in mice. The fatty acid composition of BSap and GSap was determined using gas chromatography-mass spectrometry analysis. Approximately twelve distinct fatty acids were detected in BSap and eleven in GSap. BSap showed a greater cytotoxic effect on MCF-7 cells than GSap did by inducing apoptosis and reducing inflammation, while both grape fractions had superior potency to 5-FU. Furthermore, BSap massively boosted apoptosis and lowered redox potential (Eh) and CD44+ cells in EAC cells of EAC-bearing mice more than GSap, and both fractions were more efficient than 5-FU. Blood tests and liver histopathology revealed significant improvement in EAC-induced pathological alterations with these fractions. The in silico analysis implied the competitive inhibitory impacts of the most abundant fatty acid composites in BSap and GSap on cancer-metastasis-associated proteases (cathepsin B and MMP9). Also, this analysis predicted that the apoptotic action of these Sap fractions is independent of the 5'AMP-activated protein kinase. Therefore, grape Sap-fraction, especially BSap, may be a useful agent for cancer prevention.

Genistin modulates high-mobility group box protein 1 (HMGB1) and nuclear factor kappa-B (NF-κB) in Ehrlich-ascites-carcinoma-bearing mice.

Cancer is the world's second-largest cause of death. Although there are numerous cancer treatment options, they are typically uncomfortable owing to side effects and ineffectual due to increased resistance to traditional anti-cancer medications or radiation therapy. A key method in cancer treatment is to target delayed/inhibited inflammation and apoptosis, which are very active areas of research. Natural chemicals originating from plants are of particular interest because of their high bioavailability, safety, few side effects, and, most importantly, cost-effectiveness. Flavonoids have become incredibly common as anti-cancer medications, with promising findings as cytotoxic anti-cancer agents that cause cancer cell death. Isolated compound (genistin) was evaluated for in vitro antiproliferative activity against breast cancer cell line (MCF-7 and MDA-MB-231). The compound exhibited good cytotoxic activities against both cell lines. In vivo antiproliferative efficacy was also investigated in Ehrlich's ascites carcinoma (EAC). Compared to the control group, genistin revealed a significant decrease in tumor weight, volume, high-mobility group box1 (HMGB1), and nuclear factor-kappa B (NF-κB) contents. On the other hand, B-cell lymphoma 2 (Bcl-2) contents increase suggesting an anti-inflammatory and anti-apoptotic activity through inhibition of HMGB1 signaling and activating the Bcl-2 pathway.