cyclin-d1 and Carcinoma--Ehrlich-Tumor

This study aims to investigate the potential synergistic effect of the combined treatment of galloylquinic acid compounds from Copaifera lucens with doxorubicin via the modulation of the Notch pathway in solid Ehrlich carcinoma-bearing mice model.. The solid tumor model was induced by subcutaneous inoculation of Ehrlich carcinoma cells in the right hind limb of mice, after serial syngeneic cell passages in the peritoneal cavity. Sixty mice were allocated into five groups including treated groups with galloylquinic acid compounds, doxorubicin, and their combination. Normal and tumor control groups were also assigned. Tissue homogenates were collected to measure the levels of the Notch-1, Hes-1, Jagged-1, TNF-α, IL-6 and VEGF, as well as SOD, MDA, and GSH. Histopathological and immunohistochemical examinations of tumor or control tissues were also performed for the levels of NF-κB p65, cyclin D1 and caspase 3 activity.. Our results showed that the combined treatment of galloylquinic acid compounds with doxorubicin significantly decreased the levels of the Notch-1, Hes-1, Jagged-1, TNF-α, IL-6, VEGF, NF-κB p65, and cyclin D1 in tumor tissues. Moreover, the compounds induced cancer cell death as evidence by increasing the caspase 3 activity, and they possessed potent inhibitory effects on oxidative stress.. Galloylquinic acid compounds exhibited promising antineoplastic effects and promoted the chemosensitivity of doxorubicin, mainly by modulating the Notch signaling pathway and its downstream effectors. These compounds may be considered in solid tumors treatment for improving the efficacy and reducing the side effects of chemotherapeutic agents.

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Caspase 3; Cyclin D1; Doxorubicin; Interleukin-6; Jagged-1 Protein; Mice; NF-kappa B; Signal Transduction; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Salvia lachnostachys is an herbaceous plant with anti-inflammatory, analgesic and cytotoxic properties. This study investigated the antitumor effect of an ethanolic extract of Salvia lachnostachys leaves (EES) in a solid Ehrlich carcinoma model. Ehrlich cells were inoculated subcutaneously in the right pelvic member (2 × 10

Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Carcinoma, Ehrlich Tumor; Chemoprevention; Chromatography, High Pressure Liquid; Cyclin D1; Female; Gene Expression Regulation, Neoplastic; Mice; Molecular Structure; Oxidative Stress; Plant Extracts; Plant Leaves; Reactive Oxygen Species; Salvia

The present study aimed to investigate the molecular mechanisms underlying the anticancer properties of ginger extract (GE) in mice bearing solid Ehrlich carcinoma (SEC) and to evaluate the use of GE in combination with doxorubicin (DOX) as a complementary therapy against SEC.. SEC was induced in 60 female mice. Mice were divided into four equal groups: SEC, GE, DOX and GE + DOX. GE (100 mg/kg orally day after day) and DOX (4 mg/kg i.p. for 4 cycles every 5 days) were given to mice starting on day 12 of inoculation. On the 28th day, blood samples were collected, mice were scarified, tumor volume was measured, and tumor tissues were excised.. The anti-cancer effect of GE was mediated by activation of adenosine monophosphate protein kinase (AMPK) and down-regulation of cyclin D1 gene expression. GE also showed pro-apoptotic properties as evidenced by elevation of the P53 and suppression of nuclear factor-kappa B (NF-κB) content in tumor tissue. Co-administration of GE alongside DOX markedly increased survival rate, decreased tumor volume, and increased the level of phosphorylated AMPK (PAMPK) and improved related pathways compared to DOX group. In addition, the histopathological results demonstrated enhanced apoptosis and absence of multinucleated cells in tumor tissue of GE + DOX group.. AMPK pathway and cyclin D1 gene expression could be a molecular therapeutic target for the anticancer effect of GE in mice bearing SEC. Combining GE and DOX revealed a greater efficacy as anticancer therapeutic regimen.

Topics: AMP-Activated Protein Kinases; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Apoptosis; Biomarkers, Tumor; Carcinoma, Ehrlich Tumor; Combined Modality Therapy; Cyclin D1; Dietary Supplements; Doxorubicin; Enzyme Activation; Female; Gene Expression Regulation, Neoplastic; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Mice; Necrosis; Neoplasm Proteins; Plant Extracts; Rhizome; Survival Analysis; Tumor Burden; Zingiber officinale

Since the incidence of breast cancer increases dramatically all over the world, the search for effective treatment is an urgent need. Metformin has demonstrated anti-tumorigenic effect both in vivo and in vitro in different cancer types. This work was designed to examine on molecular level the mode of action of metformin in mice bearing solid Ehrlich carcinoma and to evaluate the use of metformin in conjunction with doxorubicin as a combined therapy against solid Ehrlich carcinoma. Ehrlich ascites carcinoma cells were inoculated in 60 female mice as a model of breast cancer. The mice were divided into four equal groups: Control tumor, metformin, doxorubicin, and co-treatment. Metformin (15 mg/kg) and doxorubicin (4 mg/kg) were given intraperitoneally (i.p.) for four cycles every 5 days starting on day 12 of inoculation. The anti-tumorigenic effect of metformin was mediated by enhancement of adenosine monophosphate protein kinase activity and elevation of P53 protein as well as the suppression of nuclear factor-kappa B, DNA contents, and cyclin D1 gene expression. Metformin and doxorubicin mono-treatments exhibited opposing action regarding cyclin D1 gene expression, phosphorylated adenosine monophosphate protein kinase, and nuclear factor-kappa B levels. Co-treatment markedly decreased tumor volume, increased survival rate, and improved other parameters compared to doxorubicin group. In parallel, the histopathological findings demonstrated enhanced apoptosis and absence of necrosis in tumor tissue of co-treatment group. Metformin proved chemotherapeutic effect which could be mediated by the activation of adenosine monophosphate protein kinase and related pathways. Combining metformin and doxorubicin, which exhibited different mechanisms of action, produced greater efficacy as anticancer therapeutic regimen.

Topics: AMP-Activated Protein Kinases; Animals; Apoptosis; Breast Neoplasms; Carcinoma, Ehrlich Tumor; Cell Proliferation; Cyclin D1; Doxorubicin; Female; Gene Expression Regulation, Neoplastic; Humans; Mammary Neoplasms, Animal; Metformin; Mice; NF-kappa B; Signal Transduction; Tumor Suppressor Protein p53

Condensed-bicyclic triazolo-thiadiazoles were synthesized via an efficient "green" catalyst strategy and identified as effective inhibitors of PTP1B in vitro. The lead compound, 6-(2-benzylphenyl)-3-phenyl-[1,2,4]triazolo[3][1,3,4]thiadiazole (BPTT) was most effective against human hepatoma cells, inhibits cell invasion, and decreases neovasculature in HUVEC and also tumor volume in EAT mouse models. This report describes an experimentally unidentified class of condensed-bicyclic triazolo-thiadiazoles targeting PTP1B and its analogs could be the therapeutic drug-seeds.

Topics: Animals; Antineoplastic Agents; Benzofurans; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Caspase 3; Cell Line, Tumor; Cell Movement; Chromones; Cyclin D1; Disease Models, Animal; Dose-Response Relationship, Drug; Female; G1 Phase Cell Cycle Checkpoints; Hep G2 Cells; Human Umbilical Vein Endothelial Cells; Humans; Inhibitor of Apoptosis Proteins; Liver Neoplasms; Mice; Models, Molecular; Neoplasm Invasiveness; Neovascularization, Pathologic; Poly(ADP-ribose) Polymerases; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; STAT3 Transcription Factor; Structure-Activity Relationship; Survivin; Thiadiazoles; Triazoles

The objective of this work is to report the antiproliferative effect of P. cupana treatment in Ehrlich Ascites Carcinoma (EAC)-bearing animals. Female mice were treated with three doses of powdered P. cupana (100, 1000 and 2000 mg/kg) for 7 days, injected with 10(5) EAC cells and treated up to day 21. In addition, a survival experiment was carried out with the same protocol. P. cupana decreased the ascites volume (p = 0.0120), cell number (p = 0.0004) and hemorrhage (p = 0.0054). This occurred through a G1-phase arrest (p < 0.01) induced by a decreased gene expression of Cyclin D1 in EAC cells. Furthermore, P. cupana significantly increased the survival of EAC-bearing animals (p = 0.0012). In conclusion, the P. cupana growth control effect in this model was correlated with a decreased expression of cyclin D1 and a G1 phase arrest. These results reinforce the cancer therapeutic potential of this Brazilian plant.

Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Cycle; Cell Proliferation; Cyclin D1; Cytostatic Agents; Female; Gene Expression Regulation, Neoplastic; Mice; Mice, Inbred BALB C; Paullinia; Phytotherapy; Plant Preparations; Survival Analysis