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.

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.

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.

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.

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.

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.

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.

Evaluation of MMR live attenuated vaccine oncolytic potential using Ehrlich ascites carcinoma in a murine model.

MMR vaccine is a common vaccine that contains oncolytic viruses (Measles, Mumps, and Rubella) and could be used as a potential anti-cancer treatment. In this study, we assessed the anti-tumor activity of the MMR vaccine against Ehrlich ascites carcinoma (EAC) solid tumor induced in mice. The in vitro assay showed that vaccine IC50 in EAC was approximately 200 CCID50. The vaccine was intratumorally administrated twice weekly in EAC-bearing mice. The antitumor response of the vaccine was measured by tumor growth, survival rate, histopathologic examination, flow cytometry analysis, and body biochemical parameters. The MMR vaccine demonstrated a substantial reduction of tumor growth and prolongation of life span as well. The proliferation marker was significantly lower in the vaccine-treated group. Moreover, the apoptosis key parameter Casp-3 was also higher in the vaccine-treated group. The vaccine somewhat restored the deterioration of the biochemical parameters (LDH, GOT, GPT, MDA, NO, and PON-1) in the tumor-bearing mice. Finally, this study indicated the potential antitumor effect of MMR vaccine via anti­proliferative, apoptotic activities, and modulating the antioxidant parameters. This study opens a new field of inquiry for future research on the vaccine's anti-cancer properties.

Effect of Subchronic Selenium Treatment in the Liver of BALB/C Mice with Transplantable Ehrlich Tumor.

Selenium has an anti-inflammatory, antioxidant, and possibly antitumoral action. Thus, we hypothesized that this element could be an ally in cancer treatment. We evaluated the effect of chelated selenium treatment of BALB/c mice with Erhlich Tumor on tumor size, histology, and biochemical parameters of the liver. A total of 96 male mice were treated for 7, 15, and 30 days with different doses of chelated selenium. During the 7 days of treatment, livers presented mild hydropic degeneration; after 15 days, the livers presented mild hydropic degeneration, inflammatory infiltrate, and steatosis, which was intensified in the animals treated for 30 days. Biochemical analysis showed an increase of the alanine transaminase enzyme in those animals, indicating hepatotoxicity. At the beginning of treatment, selenium was able to inhibit tumor growth. After 30 days of treatment, however, hepatotoxicity could be seen.

[1,2,4] Triazolo [3,4-a]isoquinoline chalcone derivative exhibits anticancer activity via induction of oxidative stress, DNA damage, and apoptosis in Ehrlich solid carcinoma-bearing mice.

Despite the advances made in cancer therapeutics, their adverse effects remain a major concern, putting safer therapeutic options in high demand. Since chalcones, a group of flavonoids and isoflavonoids, act as promising anticancer agents, we aimed to evaluate the in vivo anticancer activity of a synthetic isoquinoline chalcone (CHE) in a mice model with Ehrlich solid carcinoma. Our in vivo pilot experiments revealed that the maximum tolerated body weight-adjusted CHE dose was 428 mg/kg. Female BALB/c mice were inoculated with Ehrlich ascites carcinoma cells and randomly assigned to three different CHE doses administered intraperitoneally (IP; 107, 214, and 321 mg/kg) twice a week for two consecutive weeks. A group injected with doxorubicin (DOX; 4 mg/kg IP) was used as a positive control. We found that in CHE-treated groups: (1) tumor weight was significantly decreased; (2) the total antioxidant concentration was substantially depleted in tumor tissues, resulting in elevated oxidative stress and DNA damage evidenced through DNA fragmentation and comet assays; (3) pro-apoptotic genes p53 and Bax, assessed via qPCR, were significantly upregulated. Interestingly, CHE treatment reduced immunohistochemical staining of the proliferative marker ki67, whereas BAX was increased. Notably, histopathological examination indicated that unlike DOX, CHE treatment had minimal toxicity on the liver and kidney. In conclusion, CHE exerts antitumor activity via induction of oxidative stress and DNA damage that lead to apoptosis, making CHE a promising candidate for solid tumor therapy.

Anti-proliferative and immunomodulatory potencies of cinnamon oil on Ehrlich ascites carcinoma bearing mice.

Cinnamon is a well-known natural spice and flavoring substance used worldwide. The objective of the present work is to explore the possible antitumor and immunomodulatory potencies of cinnamon essential oil (Cinn) on Ehrlich ascites carcinoma (EAC). A total of fifty female Swiss albino mice were sub-grouped into five groups (n = 10), namely, normal (a non-tumorized and non-treated) group; EAC-tumorized and non-treated group; Cinn (non-tumorized mice received Cinn, 50 mg/kg per body weight daily) group; a group of EAC-tumorized mice treated with Cinn and the final positive control group of EAC-tumorized mice received cisplatin. Eight compounds were identified from Cinn using UPLC-MS-Qtof and NMR analysis. Compared to EAC untreated group, Cinn successfully (P < 0.05) inhibited tumor growth by reducing tumor cell count (45%), viability (53%) and, proliferation accompanied by the inhibition of tumor growth rate. Moreover, a significant (P < 0.05) arrest in the cell cycle at G0/G1 phase was noticed following Cinn treatments (~ 24.5%) compared to EAC group. Moreover, Cinn markedly evoked an antitumor immune response by elevating the percentage of splenic T helper (CD3+CD4+) and T cytotoxic (CD3+CD8+) cells. It is noteworthy that Cinn treatments significantly restored different hematological alterations as well as liver and kidney functions in EAC-tumorized mice. In conclusion, results suggest that Cinn has a good antitumor and immunostimulatory potencies against Ehrlich ascites carcinoma in vivo. The mechanism underlying its antitumor activity may be attributed to its immunostimulatory effects which increase its potential as a promising anticancer candidate.

Antioxidant, cytotoxic and apoptotic activities of the rhizome of Zingiber zerumbet Linn. in Ehrlich ascites carcinoma bearing Swiss albino mice.

Due to having a long history of traditional uses as a functional food, Zingiber zerumbet was selected here to explore the inherent antioxidant and antineoplastic activities of methanolic extract of its rhizome (MEZZR) against Ehrlich ascites carcinoma (EAC) cells. The rich polyphenol containing MEZZR showed a marked DPPH, ABTS, nitric oxide radicals and lipid peroxidation inhibition activity with an IC50 of 3.43 ± 1.25, 11.38 ± 1.39, 23.12 ± 3.39 and 16.47 ± 1.47 µg/ml, respectively, when compared to the standard catechin. In vivo, MEZZR significantly inhibited EAC cell growth, decreased body weight gain, increased life span and restored the altered hematological characteristics of EAC-bearing mice. Moreover, MEZZR induced nuclear condensation and fragmentation, which are notable features of apoptosis as observed by fluorescence microscopy after staining EAC cells of MEZZR-treated mice with Hoechst 33342. Additionally, in vitro, the cell growth inhibition caused by the MEZZR in MTT assay, was remarkably decreased in the presence of caspase-3, -8 and -9 inhibitors. This study thus suggests that MEZZR may possess promising antiproliferative efficacy against EAC cells by inducing cell apoptosis.

A Newly Synthesized Derivative and a Natural Parent Molecule: Which Would Be More Beneficial as a Future Antitumor Candidate? Docking and In Vivo Study.

Seeking for new effectual anticancer drugs is of great importance. In this study, a newly synthesized and well-characterized chromene derivative (ethyl 2-amino-4-phenyl-4H-benzo(h)chromene-3-carboxylate) "C" was prepared. Molecular docking studies were done. The new compound "C" in compare to the natural parent Quercetin "Q," as a well-known natural chromene derivative with antioxidant and antitumor activities, were tested for their antitumor activity against Ehrlich ascites carcinoma (EAC)-bearing mice. Both reduced ascites volume, decreased viable EAC cells, and prolonged EAC-bearing mice life span. They normalized troponin, creatine kinase-MB, lactate dehydrogenase, and urea levels, reversed liver enzyme activities towards normal, and increased antioxidant levels while reduced tumor necrosis factor-alpha (TNF-α) levels. Compared to each other, the new synthetic derivative "C" showed stronger antineoplastic effects than the natural parent "Q" may via the anti-inflammatory activities. Therefore, the newly synthesized chromene derivative is more promising as a future antitumor candidate than the natural parent molecule "Quercetin." Finally, our results encourage researchers to pay more attention to developing more novel natural-based derivatives that would be more beneficial as future therapeutics than their natural parents.