Effects of Enoxaparin Emulsion on Dimethylbenzanthracene-induced Breast Cancer in Female Rats

Introduction: Enoxaparin is an anticoagulant medication. Anticoagulation inhibits tumor cell-mediated release of angiogenic proteins and diminishes angiogenic response. Angiogenesis is an important event in various cancers such as breast cancer. Angiogenesis provide oxygen and nutrients to tumor cells and causes tumor progression. The aim of the present study was to evaluate the anti-angiogenesis effect of an enoxaparin cream on breast cancer induced by dimethylbenzanthracene in rats. Methods: In this experimental in vivo study, 50 Wistar female rats were divided into negative control (vehicle), positive control (cream base), and 3 groups with enoxaparin treatment (40, 60, and 80 mg/ml). After one month of treatment along with breast cancer induction by dimethylbenzanthracene, breast tissue samples were isolated and stained with hematoxylin-eosin, and tumor growth suppression rate was calculated. Tumor size (length and width) was measured using a clipper, and the tumor volume was calculated using the following formula: V = (L × W × W)/2, where V is tumor volume, W is tumor width, L is tumor length. The data were analyzed using one-way ANOVA and Tukey’s post hoc test. Results: Tumor suppression was significantly increased in enoxaparin treatment groups compared to the positive control group (40 mg/ml of enoxaparin treated versus positive control group; P = 0.017, 60 mg/ml of enoxaparin treated versus positive control; P = 0.015, 40 mg/ml of enoxaparin treated versus positive control; P = 0.009, 60 mg/ml of enoxaparin treated versus 40 mg/ml of enoxaparin treated; P = 0.019, and 80 mg/ml of enoxaparin treated versus 40 mg/ml of enoxaparin treated; P = 0.011 in a dose-dependent manner. Conclusion: Enoxaparin inhibits breast cancer in a dose-dependent manner. The application of enoxaparin cream in patients with breast cancer may considerably reduce tumor growth.

Download Full-text

Effect of Black Seed (Nigella sativa) and Uziza (Piper guineense) Leaf on the Histology of the Liver of Wistar Albino Rats

Biotechnology Journal International ◽

10.9734/bji/2019/v23i230075 ◽

2019 ◽

pp. 1-11

Author(s):

Okoye Ngozi Franca ◽

Ikiriko, Favour Ibiwari

Keyword(s):

Aqueous Extract ◽

Nigella Sativa ◽

Positive Control ◽

Negative Control ◽

Positive Control Group ◽

Control Group ◽

Dependent Manner ◽

Piper Guineense ◽

The Third ◽

Black Seed

Aim: This study was aimed at investigating the effects of aqueous extracts of both Nigella sativa and Piper guineense on the liver enzymes; alanine amino transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase (ALP). Also the effect of Nigella sativa and Piper guineense extracts on the histology of the liver of Wistar rat was also studied. Materials and Methods: A total of twenty five Wistar rats were used for the study. The animals were grouped into five groups, each having five animals. They were induced with sucrose and margarine to cause high sugar levels and hyperlipidemia respectively except the positive control group which was fed normal feed. The groups were: the positive control group, the negative control group which were induced without treatment, the uziza leaf group which were induced and were treated with 2 ml of aqueous extract of uziza leaf, the black seed group which were induced and were treated with 2 ml of aqueous extract of black seed, and the black seed and uziza group which were induced and were treated with 2ml of aqueous extract of black seed and 2 ml of aqueous extract of uziza leaf. Results: The result showed that the extracts decreased the ALT and AST and ALP activities in the rats in a time dependent manner with highest decrease obtained on the third week of treatment with the extracts. The ALT activity (U/L) on the third week of treatment showed for the, negative control (64.48 ± 0.22), uziza leaf (28.82 ± 0.12), black seed (32.65 ± 0.02), black seed and uziza leaf (16.04 ± 0.02) (p≤0.05). The decrease in activity for AST levels (U/L) on the third week of treatment, showed for the negative control (58.00 ± 0.02), uziza leaf (11.00 ± 0.01), black seed (12.00 ± 0.02), black seed and uziza leaf (8.00 ± 0.02). Conclusion: It can be concluded that both uziza leaf and black seed have hepatoprotective effect on the liver.

Download Full-text

In VivoAntiplasmodial and Analgesic Effect of Crude Ethanol Extract ofPiper guineenseLeaf Extract inAlbinoMice

Scientifica ◽

10.1155/2016/8687313 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

A. Y. Kabiru ◽

G. F. Ibikunle ◽

D. A. Innalegwu ◽

B. M. Bola ◽

F. M. Madaki

Keyword(s):

Body Weight ◽

Analgesic Efficacy ◽

Ethanol Extract ◽

Positive Control ◽

Positive Control Group ◽

Control Group ◽

Piper Guineense ◽

Standard Drug ◽

Analgesic Effects ◽

Dose Dependent

Antiplasmodial and analgesic effects of crude ethanol extract ofPiper guineensewas investigated in mice. The antiplasmodial and analgesic efficacy of the extract was judged on its ability to reduce parasitemia and writhing, respectively, in mice. The antiplasmodial screening involved treating infected mice with 200, 400, and 600 mg/kg body weight of extract while the positive control group was given standard artesunate drug. The analgesic test was carried out by administering 1000, 1500, and 2000 mg/kg body weight of extract to three groups of healthy mice, respectively, after induction of pain with 0.75% acetic acid. The positive control group was given aspirin drug. Parasitemia was reduced by 28.36%, 43.28%, and 62.69% in a dose-dependent pattern in the curative test which was significantly different (P<0.05) from 96.03% of the standard drug. The reduction of writhing by mice given the extract was also dose-dependent (36.29, 45.43, and 59.07%). Aspirin drug was however more effective (86.36%). The extract was safe at 2000 mg/kg body weight. Phytochemical screening revealed the presence of flavonoids, tannins, phlobatannins, terpenoids, and coumarins. Result obtained in this study demonstrated the efficacy of ethanol extract ofPiper guineenseas an antiplasmodial and analgesic agent.

Download Full-text

Promoting effect of Se-allylselenocysteine on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis

Journal of Food Bioactives ◽

10.31665/jfb.2020.9221 ◽

2020 ◽

Vol 9 ◽

Author(s):

An-Chin Cheng ◽

Wan-Ru Jiang ◽

Yu-Hsuan Hsiao ◽

Vladimir Badmaev ◽

Chi-Tang Ho ◽

...

Keyword(s):

Nitric Oxide ◽

Positive Control ◽

Positive Control Group ◽

Raw 264.7 Cells ◽

Control Group ◽

Dependent Manner ◽

Promoting Effect ◽

Skin Tumorigenesis ◽

Cox 2 ◽

Anti Inflammatory

Se-allylselenocysteine (ASC), an analogue of garlic compound, has been shown to inhibit mammary carcinogenesis in vivo and cell growth in vitro. However, the function of ASC on anti-inflammatory effects remains largely unknown. Therefore, we investigated whether ASC has an anti-inflammatory effect on lipopolysaccharide (LPS) -induced inflammation or an anti-tumour effect promoting on DMBA/TPA-induced skin tumorigenesis and tried to elucidate the mechanisms involved. Herein, the results showed that ASC inhibited LPS-induced production of nitric oxide (NO) with a decreased protein level of inducible nitric oxide synthase (iNOS) in RAW 264.7 cells. However, ASC enhanced LPS-induced cyclooxygenase-2 (COX-2) protein levels and mRNA expression. Interestingly, we found for the first time that topical application of ASC on the dorsal skin of DMBA-initiated and TPA-promoted mice significantly accelerated skin tumorigenesis and raised tumour multiplicity as compared to the positive control group (DMBA/TPA). The number of tumours that were 1–3 mm, 3–5 mm, and >5 mm in size per mouse increased in a dose-dependent manner in the ASC pre-treated groups. Pre-treatment with ASC showed a significant increase in the expression of COX-2 compared with the positive control group. In summary, that ASC may modulate the COX-2 protein expression and promoting DMBA/TPA-induced skin cancer in mice.

Download Full-text

Antagonist Anti-CD40 Antibody CHIR-12.12 Causes Tumor Regression and Prolongs Survival in Multiple Myeloma Xenograft Models.

Blood ◽

10.1182/blood.v104.11.4888.4888 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4888-4888

Author(s):

Li Long ◽

Xia Tong ◽

Montesa Patawaran ◽

Lea Aukerman ◽

Bahija Jallal ◽

...

Keyword(s):

Multiple Myeloma ◽

Tumor Growth ◽

Tumor Cells ◽

Tumor Volume ◽

Dependent Manner ◽

Human Multiple Myeloma ◽

Xenograft Models ◽

Dose Dependent

Abstract CD40 is expressed on most B cell malignancies including multiple myeloma and represents an attractive target for antibody therapy. We have generated a novel, highly potent, fully human antagonistic anti-CD40 monoclonal antibody, CHIR-12.12, using XenoMouse® mice (Abgenix, Inc). The antibody can mediate anti-tumor activity potentially by at least two mechanisms: CHIR-12.12 can block CD40-ligand mediated survival signals and it can lyse tumor cells by antibody-dependent cellular cytotoxicity (ADCC). We have previously reported that CHIR-12.12 mediates stronger killing of CD40- and CD20-expressing lymphoma cells than rituximab by ADCC in vitro and significantly inhibits the growth of both rituximab-responsive and rituximab-resistant human lymphoma xenografts in vivo. In this study, we examined in vitro and in vivo efficacy of CHIR-12.12 against human multiple myeloma. The human MM cell line IM-9, which expresses both CD40 and CD20, the target antigen for CHIR-12.12 and rituximab respectively was used for the study. CHIR-12.12 induced lysis of target tumor cells by ADCC in a dose dependent manner reaching maximum cell lysis at 0.1ug/ml concentration. The maximum specific lysis of IM-9 cells by CHIR-12.12 was greater than the lysis induced by rituximab (64% vs 45 %, n=3, p<0.01). In addition, the EC50 of CHIR-12.12 was on average 5.9 picomolar, which was 10-fold lower than the EC50 of rituximab. Greater ADCC by CHIR-12.12 was not due to higher density of CD40 molecules on the target tumor cells compared to CD20 molecules. IM-9 cells expressed 35590 ±8858 CD40 molecules compared to 93783 ± 2247 CD20 molecules. The in vivo CHIR-12.12 efficacy was then evaluated in IM-9 xenograft model. In an un-staged conditional survival model, where treatment began one day after intravenous inoculation of IM-9 tumor cells, CHIR-12.12 significantly prolonged the survival of tumor-bearing mice in a dose-dependent manner with 60% survival in the 0.1 mg/kg CHIR-12.12 treated group and 80% survival in the 1 and 10 mg/kg groups respectively on day 56 (Log Rank Test: P<0.01 and P<0.001, respectively). All animals in the control IgG1 and bortezomib treated groups were terminated between day 18 and day 26 due to severe disease related to tumor development (i.e., hind limb paralysis and significant body weight loss). In a staged subcutaneous model, where treatment began once the tumor volume was 150–200mm3, CHIR-12.12 administered weekly at 0.1, 1 and 10 mg/kg significantly inhibited tumor growth with a tumor volume reduction of 17% (P>0.05), 34% (P<0.01) and 44% (P<0.001) respectively. Bortezomib, when tested at 0.5 mg/kg twice a week did not inhibit tumor growth. At the maximally tolerated dose (MTD) of 1 mg/kg twice a week, bortezomib inhibited tumor growth by 30% (P<0.01). Taken together, these data demonstrate that the anti-CD40 mAb CHIR-12.12 has potent activity against human multiple myeloma in vitro and xenograft models in vivo.

Download Full-text

Anti-proliferative Activities of Two Flavonols with Unsubstituted B-ring from the Leaves of Platanus acerifolia

Natural Product Communications ◽

10.1177/1934578x1701201110 ◽

2017 ◽

Vol 12 (11) ◽

pp. 1934578X1701201

Author(s):

Hui-Feng Chen ◽

Ri-Zhen Huang ◽

Bo Zuo ◽

Lan-Ju Ji ◽

Zhi-Jian Mo ◽

...

Keyword(s):

Ethanol Extract ◽

Positive Control ◽

Control Group ◽

Dependent Manner ◽

Hoechst 33258 ◽

Caspase 9 ◽

Platanus Acerifolia ◽

Anti Cancer ◽

Cellular Apoptosis ◽

Dose Dependent

The anti-proliferative activities against five cancer cell lines of two flavonols (1, 2) with unsubstituted B ring isolated from the ethanol extract of the leaves of Platanus acerifolia were investigated. The results showed that compound 1 possessed a noteworthy anti-proliferative activity against MGC-803 cells with an IC50 value of 17.26±1.04 μM, and compound 2 was less active than 1 with an IC50 value of 20.29±1.37 μM compared with 41.94±1.58 μM for the positive control group. In addition, the results of Hoechst 33258 staining, AO/EB staining and annexinV-FITC assays indicated that 1 caused a significant MGC-803 cellular apoptosis in a dose-dependent manner. The further mechanisms showed that compound 1 induced the production of ROS, decreased the mitochondrial membrane potential, and altered pro- and anti-apoptotic proteins, leading to activation of caspase-9 and caspase-3 in the process of cellular apoptosis. The present investigation indicated that compound 1 could be used as a potential anti-cancer candidate.

Download Full-text

The Anti-Breast Cancer Effects of Green-Synthesized Zinc Oxide Nanoparticles Using Carob Extract

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200721132522 ◽

2020 ◽

Vol 20 ◽

Author(s):

Vahid Pouresmaeil ◽

Shaghayegh Haghighi ◽

Asieh S. Raeisalsadati ◽

Ali Neamati ◽

Masoud Homayouni-Tabrizi

Keyword(s):

Breast Cancer ◽

Zinc Oxide ◽

Zinc Oxide Nanoparticles ◽

Quantitative Polymerase Chain Reaction ◽

Breast Cancer Cell Lines ◽

Control Group ◽

Oxide Nanoparticles ◽

Dependent Manner ◽

Zno Nps ◽

Dose Dependent

Background: The use of nanoparticles synthesized by the green method to treat cancer is fairly recent. The aim of this study was to evaluate cytotoxicity, apoptotic and anti-angiogenic effects and their expression of involving genes, of zinc oxide nanoparticles (ZnO-NPs) synthesized with Carob extract on different human breast cancer cell lines. Methods: ZnO-NPs synthesized using the extract of Carob and characterized with various analytical techniques. The MCF-7 and MDA-MB231 cells were treated at different times and concentrations with ZnO-NPs. The cytotoxicity, apoptosis and anti-angiogenic were examined using a series of cellular assays. Expression of apoptotic genes (Bax and Bcl2) and anti-angiogenic genes, vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) in cancer cells treated with ZnO-NPs were examined with Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The antioxidant activities of ZnO-NPs evaluated by ABTS and DPPH assay. Results: Exposure of cells to ZnO-NPs resulted in a dose-dependent loss of cell viability. The IC50 at 24, 48 and 72 hours were 125, 62.5 and 31.2µg/ml respectively (p<0.001). ZnO-NPs treated cells showed in fluorescent microscopy that ZnONPs are able to upregulate apoptosis and RT-qPCR revealed upregulation of Bax (p<0.001) and downregulation of Bcl-2 (p<0.05). ZnO-NPs increased VEGF gene expression while decreasing VEGF-R (p<0.001). The antioxidant effects of ZnO-NPs were higher than control group and were dose dependent manner (p<0.001). Conclusion: ZnO-NPs synthetized using Carob extract have the ability to eliminate breast cancerous cells and inhibit angiogenesis so could be used as anticancer agent.

Download Full-text

Resistance to Fracture of Dental Roots Obturated with Different Materials

BioMed Research International ◽

10.1155/2015/591031 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Berkan Celikten ◽

Ceren Feriha Uzuntas ◽

Kamran Gulsahi

Keyword(s):

Fracture Resistance ◽

Testing Machine ◽

Negative Control Group ◽

Positive Control ◽

Negative Control ◽

Positive Control Group ◽

Control Group ◽

Root Canal Filling ◽

Filling Materials ◽

Group 2

The aim of this study was to compare the vertical fracture resistance of roots obturated with different root canal filling materials and sealers. Crowns of 55 extracted mandibular premolar teeth were removed to provide root lengths of 13 mm. Five roots were saved as negative control group (canals unprepared and unfilled). Fifty root canals were instrumented and then five roots were saved as positive control group (canals prepared but unfilled). The remaining 45 roots were randomly divided into three experimental groups (n=15root/group) and obturated with the following procedures: in group 1, glass ionomer-based sealer and cone (ActiV GP obturation system); in group 2, bioceramic sealer and cone (EndoSequence BC obturation system); and in group 3, roots were filled with bioceramic sealer and cone (Smartpaste bio obturation system). All specimens were tested in a universal testing machine for measuring fracture resistance. For each root, the force at the time of fracture was recorded in Newtons. The statistical analysis was performed by using Kruskal-Wallis and post hoc test. There were no significant differences between the three experimental groups. The fracture values of three experimental and negative control groups were significantly higher than the positive control group. Within the limitations of this study, all materials increased the fracture resistance of instrumented roots.

Download Full-text

Antidiabetic and antihyperlipidemic activities of Cucumis melo var. momordica fruit extract on experimental animals

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-020-00116-z ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Arvind Kumar Srivastava ◽

Alok Mukerjee ◽

Abhishek Tripathi

Keyword(s):

Blood Glucose ◽

Cucumis Melo ◽

Biological Properties ◽

Positive Control ◽

Positive Control Group ◽

Public Health Issue ◽

Control Group ◽

Fruit Extract ◽

Experimental Animals ◽

Glucose Levels

Abstract Background Diabetes mellitus is a major public health issue related to the irregular metabolism of carbohydrates, protein, and fat. It occurs due to insufficient insulin production and insulin action. Cucumis melo possesses several biological properties including antioxidant, anti-inflammatory, antibacterial, antihypothyroidism, and antiangiogenic activities. The objective of the present study was to determine the antidiabetic and antihyperlipidemic activities of Cucumis melo var. momordica fruit extract on experimental animals. Result Results show that treatment with C. melo fruit extract and fraction caused a reduction in blood glucose levels. Cucumis melo toluene fraction (CMTF) exhibited a significant (*P < 0.05) reduction of blood glucose level on the 28th day, i.e., 122 mg/dL, in comparison with the positive control group (streptozotocin (STZ)). However, the extract of C. melo showed less significant results in comparison with CMTF. Triglyceride, LDL, and VLDL levels were increased chronically due to STZ and were significantly (*P < 0.05) restored to 84.16, 86.97, and 19.73, respectively, by CMTF in comparison with the positive control group (STZ in the dose of 55 mg/kg). The extract-treated groups also showed similar results as CMTF, but their efficacy was lesser than CMTF. Conclusion It is can be concluded that C. melo fruits can be used as an effective antidiabetic and antihyperlipidemic drug. Graphical abstract

Download Full-text

Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽

10.3390/pharmaceutics13030386 ◽

2021 ◽

Vol 13 (3) ◽

pp. 386

Author(s):

Tung-Hu Tsai ◽

Yu-Jen Chen ◽

Li-Ying Wang ◽

Chen-Hsi Hsieh

Keyword(s):

Stereotactic Body Radiation Therapy ◽

In Vivo Studies ◽

Control Group ◽

High Dose ◽

Dependent Manner ◽

Hep G2 ◽

Time Curve ◽

Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

Download Full-text

Effect of lemon peel flavonoids on anti-fatigue and anti-oxidation capacities of exhaustive exercise mice

Applied Biological Chemistry ◽

10.1186/s13765-020-00573-3 ◽

2020 ◽

Vol 63 (1) ◽

Author(s):

Guili Bao ◽

Yinglong Zhang ◽

Xiaoguang Yang

Keyword(s):

Skeletal Muscle ◽

Superoxide Dismutase ◽

Manganese Superoxide Dismutase ◽

Fatty Acid Content ◽

Hepatic Tissue ◽

Control Group ◽

Dependent Manner ◽

Lemon Peel ◽

Tnf Α ◽

Dose Dependent

AbstractIn this study, lemon peel flavonoids (LPF) were administered to investigate its effect on the anti-fatigue and antioxidant capacity of mice that undergo exercise until exhaustion. LPF (88.36 min in LPFH group mice) significantly increased the exhaustion swimming time compare to the untreated mice (40.36 min), increased the liver glycogen and free fatty acid content in mice and reduce lactic acid and BUN content in a dose-dependent manner. As the concentration of lemon peel flavonoids increased, the serum creatine kinase, aspartate aminotransferase, and alanine aminotransferase levels of mice gradually decreased. LPF increases superoxide dismutase (SOD) and catalase (CAT) levels in mice and reduces malondialdehyde levels in a dose-dependent manner. And LPF raises hepatic tissue SOD, CAT activities and reduces skeletal muscle tissue iNOS, TNF-α levels of mice compared to the control group. LPF also enhanced the expression of copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and CAT mRNA in mouse liver tissue. LPF also enhanced the expression of alanine/serine/cysteine/threonine transporter 1 (ASCT1) mRNA and attenuate the expression of syncytin-1, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α in mouse skeletal muscle. According to high-performance liquid chromatography (HPLC) analysis, it was found that LPF contains flavonoids such as rutin, astragalin, isomangiferin, naringin, and quercetin. Our experimental data show that LPF has good anti-fatigue effects and anti-oxidation ability. In summary, LPF has high prospects to be developed and added to nutritional supplements.

Download Full-text