scholarly journals Ethoxyquin Inhibits the Progression of Murine Ehrlich Ascites Carcinoma through the Inhibition of Autophagy and LDH

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1526
Author(s):  
Fekria Tayel ◽  
Magdy E. Mahfouz ◽  
Afrah F. Salama ◽  
Mohammed A. Mansour
Keyword(s):  
Cancer Cells ◽  
Krebs Cycle ◽  
Lactate Production ◽  
Ehrlich Ascites Carcinoma ◽  
Cancer Models ◽  
Ehrlich Ascites ◽  
Preclinical Trials ◽  
Atp Generation ◽  
Hematological And Biochemical Parameters ◽  
Eac Cells

Cancer cells exhibit an increased glycolysis rate for ATP generation (the Warburg effect) to sustain an increased proliferation rate. In tumor cells, the oxidation of pyruvate in the Krebs cycle is substituted by lactate production, catalyzed by LDH. In this study, we use ethoxyquin (EQ) as a novel inhibitor to target LDH in murine Ehrlich ascites carcinoma (EAC) and as a combination therapy to improve the therapeutic efficacy of the conventional chemotherapy drug, cisplatin (CIS). We investigated the anti-tumor effect of EQ on EAC-bearing mice and checked whether EQ can sustain the anti-tumor potential of CIS and whether it influences LDH activity. Treatment with EQ had evident anti-tumor effects on EAC as revealed by the remarkable decrease in the expression of the anti-apoptotic gene Bcl-2 and by a significant increase in the expression of apoptotic genes (BAX and caspase-3). EQ also caused a significant decrease in the autophagic activity of EAC cells, as shown by a reduction in the fluorescence intensity of the autophagosome marker. Additionally, EQ restored the altered hematological and biochemical parameters and improved the disrupted hepatic tissues of EAC-bearing mice. Co-administration of EQ and CIS showed the highest anti-tumor effect against EAC. Collectively, our findings propose EQ as a novel inhibitor of LDH in cancer cells and as a combinatory drug to increase the efficacy of cisplatin. Further studies are required to validate this therapeutic strategy in different cancer models and preclinical trials.

Tumor cell metabolism in vitro: a study of incubation media

1970 ◽  
Vol 48 (4) ◽  
pp. 517-519 ◽  
Author(s):  
I. C. Caldwell ◽  
Marianne F. Chan
Keyword(s):  
Nucleic Acid ◽  
Structural Integrity ◽  
Cell Metabolism ◽  
Ehrlich Ascites Carcinoma ◽  
Leukemic Cells ◽  
Prolonged Incubation ◽  
Ehrlich Ascites ◽  
Eac Cells ◽  
Rna And Dna

A number of incubation media which have been used in studies of the metabolism of Ehrlich ascites carcinoma (EAC) cells in vitro have been examined with respect to their abilities to support the incorporation of radioactive precursors into nucleotides and nucleic acids, and to maintain the structural integrity and tumor-inducing abilities of EAC cells. Cells incubated in the chemically-defined "Fischer's medium for leukemic cells of mice" were able to produce lethal tumors in mice after more than 16 h of incubation, maintained their structural integrity on prolonged incubation, and catalyzed high rates of incorporation of exogenously added substrates into nucleotides, RNA, and DNA. However, cells incubated in balanced salts solutions supplemented with glucose had these characteristics: (a) were unable to produce lethal tumors after 4 h of incubation, (b) released large amounts of nucleotide, nucleic acid, and protein material into the medium after less than 2 h of incubation, and (c) catalyzed the incorporation of radioactive precursors into nucleotides and RNA at much lower rates than did cells incubated in Fischer's medium, and were virtually unable to catalyze the incorporation of adenine-14C into DNA.

Evaluation of Cisplatin Combined with Ondansetron in Ehrlich Ascites Carcinoma in Vitro and in Vivo

2000 ◽  
Vol 86 (2) ◽  
pp. 153-156 ◽  
Author(s):  
Osama Ahmed Badary ◽  
Sahar Moustafa Sharaby ◽  
Sanaa Abd El-Baky Kenawy ◽  
Ezz El-Deen El-Denshary ◽  
Farid Mohamed Ahmed Hamada
Keyword(s):  
Antitumor Activity ◽  
Ehrlich Ascites Carcinoma ◽  
Host Tissue ◽  
Nausea And Vomiting ◽  
Single Treatment ◽  
Blood Cell Count ◽  
Ehrlich Ascites ◽  
Eac Cells

Aims and background Nausea and vomiting occur in the majority of patients receiving cisplatin (CDDP) chemotherapy. Ondansetron, a new 5-HT3 receptor antagonist, has been used effectively to control CDDP-induced nausea and vomiting. This study examined the potential of ondansetron to interfere with CDDP antitumor activity and toxicity in Ehrlich ascites carcinoma (EAC). Methods The influence of ondansetron on CDDP cytotoxicity was evaluated using EAC cells in culture. In addition, the influence of ondansetron pretreatment on CDDP-induced antitumor activity and host tissue toxicity was studied in EAC-bearing mice. Results Ondansetron (0.25 μM) enhanced CDDP (0–32 μM) cytotoxicity against EAC cells in vitro. In EAC-bearing mice ondansetron (0.2 mg/kg, ip) administered 1 h before CDDP (7 mg/kg, ip) did not modify the antitumor activity of CDDP. CDDP (7 mg/kg, ip) single treatment induced significant increases in blood urea nitrogen (2-fold) and serum creatinine (2.5-fold) and significant decreases in hematocrit (25%) and white blood cell count (39%) compared to saline treatment. Mice receiving ondansetron 1 h before CDDP showed no significant enhancement of CDDP-induced nephrotoxicity or myelosuppression compared to those pretreated with saline receiving the same dose of CDDP. Conclusions This study suggests that the use of ondansetron to control CDDP-induced nausea and vomiting does not affect CDDP antitumor efficacy.

Trema orientalis (Linn.) leaves promotes anticancer activity in Ehrlich ascites carcinoma (EAC) in Swiss albino mice

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Masnoon Kabir ◽  
Abdullah AL-Noman ◽  
Biplab Kumar Dash ◽  
Mahmudul Hasan ◽  
Shahina Akhter ◽  
...  
Keyword(s):  
Body Weight ◽  
Tumor Cell ◽  
Chromatin Condensation ◽  
Hematological Parameters ◽  
Ehrlich Ascites Carcinoma ◽  
Swiss Albino Mice ◽  
Ehrlich Ascites ◽  
Trema Orientalis ◽  
Albino Mice ◽  
Eac Cells

AbstractBackgroundThe in vivo anticancer effect of the Trema orientalis leaves crude methanol extract (TLME) was screened against Ehrlich ascites carcinoma (EAC) in Swiss albino mice.Materials and methodsThe cytotoxic activity of TLME was determined in vitro by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The growth inhibitory activity and morphological alterations were determined by the hemocytometer counting of the EAC cells using trypan blue dye. The apoptotic cells were assessed by DAPI (4′,6-diamidino-2-phenylindole) staining. The hematological and biochemical parameters of experimental mice were also estimated.ResultsAfter treatment with the TLME, the viable tumor cell count, morphological changes and nuclear damages of the EAC cells were observed along with the hematological parameters of the experimental mice. The LD50 of TLME was 3120.650 mg/kg body weight, and this extract was proven to be safe at a dose of as high as 800 mg/kg body weight. The oral administration of the TLME at 400 mg/kg body weight resulted in approximately 59% tumor cell growth inhibition compared with the control mice, with considerable apoptotic features, including membrane blebbing, chromatin condensation, nuclear fragmentation and aggregation of the apoptotic bodies in DAPI staining under a fluorescence microscope. The TLME also dose-dependently restored the altered hematological parameters to approximately normal levels. The TLME exhibited bolstering cytotoxic effect against the EAC cell with the IC50 value of 29.952 ± 1.816 μg/mL.ConclusionThe TLME has potential as a natural anti-cancer product with apoptosis induction property and cytotoxicity against carcinoma cells.

scholarly journals In vivo Anticancer Activity on Ehrlich Ascites Carcinoma (EAC) Cells and in vitro Antimicrobial Activity of Psidium guajava Bark Extracts

2019 ◽  
Vol 35 (1) ◽  
pp. 79-81
Author(s):  
Md Jakir Hossain ◽  
Shashwata Biswas ◽  
Mohammad Shahriar ◽  
Sohidul Islam ◽  
Chowdhury Rafiqul Ahsan
Keyword(s):  
Antimicrobial Activity ◽  
Anticancer Activity ◽  
Methanol Extract ◽  
Ehrlich Ascites Carcinoma ◽  
Psidium Guajava ◽  
Negative Control ◽  
Ehrlich Ascites ◽  
Eac Cells

This study was performed to evaluate the in vivo anticancer activity against ehrlich ascites carcinoma (EAC) cells and in vitro antimicrobial activity of Psidium guajava bark extracts. By soxhlet apparatus, the P. guajava bark extracts were obtained using four solvents (n-hexane, petroleum benzene, chloroform, and methanol) according to their increasing solubility. In case of in vivo anticancer activity of the sample extracts, mice were seeded with approximately 1x105 ehrlich ascites carcinoma (EAC) cells. After seven days of consecutive treatment, the negative and positive control groups (n=8 each group) showed an average EAC cell count of 2.4x108 and 1.8x108 respectively, and the experimental groups showed the cell count of 2.2x 108, 2.1x108, 1.9x108, and 1.41x108 when mice received h-hexane, petroleum benzene, chloroform, and methanol extract respectively. Experimental group that received methanol extract showed percent increase of life span (% ILS) of 33.3 when compared with the negative control. However, treatment in a cyclic manner of the mice showed % ILS of 52.15 for experimental group when compared negative control. In antimicrobial activity experiment, an intermediate zone of sensitivity of the crude methanol extract was found against Escherichia coli, Shigella flexneri, and Staphylococcus aureus when compared with amoxicillin. All these results indicated the anticancer activity and antimicrobial activity of the methanol extract of P. guajava barks on different experimental models. Bangladesh J Microbiol, Volume 35 Number 1 June 2018, pp 79-81

Photo-extracellular synthesis of gold nanoparticles using Baker's yeast and their anticancer evaluation against Ehrlich ascites carcinoma cells

2016 ◽  
Vol 40 (11) ◽  
pp. 9395-9402 ◽  
Author(s):  
Yasser A. Attia ◽  
Yassmeen E. Farag ◽  
Yasser M. A. Mohamed ◽  
Akaber T. Hussien ◽  
Tareq Youssef
Keyword(s):  
Gold Nanoparticles ◽  
Visible Light ◽  
Cancer Cells ◽  
Yeast Extract ◽  
Ehrlich Ascites Carcinoma ◽  
Carcinoma Cells ◽  
Baker's Yeast ◽  
Extracellular Synthesis ◽  
Ehrlich Ascites ◽  
Highly Effective

Novel gold nanoparticles capped by yeast extract, showing highly effective cytotoxicity towards cancer cells under visible light.

Suppression of molecular targets and antiproliferative effect of citronellal in triple-negative breast cancer cells

2021 ◽  
Vol 14 ◽  
Author(s):  
Kaneez Fatima ◽  
Suaib Luqman
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Molecular Targets ◽  
Ehrlich Ascites Carcinoma ◽  
Antiproliferative Effect ◽  
Ehrlich Ascites

Background: Triple-negative breast cancer (TNBC) requires targeted therapies to better manage and prevent metastatic mammary gland tumors. Due to the resistance problem associated with the approved drugs, researchers are now focusing on phytochemicals for the treatment of TNBC as they possess a pleiotropic mode of action and fewer side effects. Objective: To investigate the antiproliferative effect of citronellal in triple negative breast cancer cells. Method: Anticancer potential of citronellal was explored by employing SRB, MTT and NRU antiproliferative assay. Further, the effect of citronellal was observed on molecular targets (Tubulin, COX-2 and LOX-5) utilizing in vitro and in silico methods. Furthermore, the efficacy of citronellal was examined on Ehrlich Ascites Carcinoma. In addition, the safety profiling of it was observed at 300 and 1000 mg/kg of body weight in mice. Results: Citronellal suppresses the growth of MDA-MB-231 cells by more than 50% in NRU assay and ~41% and 32% in SRB and MTT assay, respectively. Further, citronellal's effect was observed on molecular targets wherein it suppressed LOX-5 activity (IC50 40.63±2.27 µM) and prevented polymerization of microtubule (IC50 63.62 µM). The result was more prominent against LOX-5 as supported by molecular docking interaction studies, but a non-significant effect was observed at the transcriptional level. The efficacy of citronellal was also determined in Ehrlich Ascites Carcinoma (EAC) model, wherein it inhibited the growth of tumor cells (45.97%) at 75 mg/kg of body weight. It was non-toxic upto 1000 mg/kg of body weight in mice and did not cause significant lysis of erythrocytes. Conclusion: These observations could provide experimental support for citronellal to be used as a chemopreventive agent for breast cancer.

2', 4'-dihydroxy-3, 4-methylenedioxychalcone Activate Mitochondrial Apoptosis of Ehrlich Ascites Carcinoma Cells

2020 ◽  
Vol 15 (4) ◽  
pp. 337-350
Author(s):  
Mahbuba Khatun ◽  
Farhadul Islam ◽  
Vinod Gopalan ◽  
Md. Motiar Rahman ◽  
Natasha Zuberi ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Chromatin Condensation ◽  
In Vitro Study ◽  
Ehrlich Ascites Carcinoma ◽  
Dependent Manner ◽  
Anticancer Properties ◽  
Ehrlich Ascites ◽  
Induced Apoptosis ◽  
Eac Cells

Background: Development of effective cancer-chemotherapy is the most challenging field due to the toxicity of chemo-agents. Objective: As chalcone has been known to have pharmacological applications, here the aim is to synthesized three chalcone derivatives, 2',4'-dihydroxy-3,4-methylenedioxychalcone (C1), 2'-hydroxy- 2,4, 6-trimethoxychalcone (C2) and 2'-hydroxy-4-methylchalcone (C3) and investigate their anti-cancer properties against Ehrlich Ascites Carcinoma (EAC) cell. Method: Anticancer properties against EAC cells were studied by examining growth inhibition, MTT assays, tumour-bearing mice survival, tumour weight measurement and haematological profiles. Moreover, apoptosis of EAC cells was investigated by fluorescence microscopy, flowcytometry and DNA fragmentation assays. Expression of apoptosis related genes were studied by reverse transcriptase-PCR (RT-PCR). Results: Among the compounds, C1 exhibited highest cell growth inhibition at 200 mg/kg/day (81.71%; P < 0.01). C1 treatment also increased the life span of EAC-bearing mice (82.60%, P < 0.05) with the reduction of tumour burden (22.2%, P < 0.01) compared to untreated EAC-bearing mice. In vitro study indicated that C1 killed EAC-cells in a dose-dependent manner and induced mitochondria-mediated apoptotic pathways. In addition, C1 treated cells exhibited increased apoptotic features such as membrane blebbing, chromatin condensation, and nuclear fragmentation after Hoechst 33342 staining. Increased fragmentation of DNA in gel electrophoresis followed by C1 treatment further confirmed apoptosis of EAC cells. EAC cells treated with C1 showed reduced Bcl-2 expression in contrast to notable upregulation of p53 and Bax expression. It implied that C1 could reinstate the expression of pro-apoptotic tumour suppressor and inhibit anti-apoptotic genes. Conclusions:: Thus, C1 showed significant growth inhibitory properties and induced apoptosis of EAC cells.

RESISTANCE TO PURINE RIBONUCLEOSIDE ANALOGUES IN AN ASCITES TUMOR

1967 ◽  
Vol 45 (5) ◽  
pp. 735-744 ◽  
Author(s):  
Ian C. Caldwell ◽  
J. Frank Henderson ◽  
A. R. P. Paterson
Keyword(s):  
De Novo ◽  
Repeated Administration ◽  
Ehrlich Ascites Carcinoma ◽  
Similar Degree ◽  
Inhibitory Effects ◽  
Resistant Variant ◽  
Growth Inhibitory ◽  
Ehrlich Ascites ◽  
Derivatives Of ◽  
Eac Cells

A tumor subline (EAC-R2) which is resistant to the growth-inhibitory effects of 6-(methylmercapto)purine ribonucleoside (Me6MPR) and formycin has been selected from the Ehrlich ascites carcinoma (EAC) by repeated administration of Me6MPR during the propagation of the tumor. Some biochemical characteristics of the two tumor lines have been compared.Cells of the EAC-R2 tumor could not form phosphorylated derivatives of Me6MPR and formycin, whereas these metabolites were readily formed by EAC cells. Extracts of the resistant cells could not convert Me6MPR to the 5′-phosphate, indicating that they were deficient in purine ribonucleoside kinase activity.Me6MPR, formycin, and several other purine nucleoside analogues produced much less inhibition of purine synthesis de novo in EAC-R2 cells than in the parent line of cells. However, adenine produced a similar degree of inhibition in both tumor lines, indicating that this pathway in the resistant variant is susceptible to feedback inhibition.It is proposed that a deficiency of purine ribonucleoside kinase(s) may be responsible for the inability of Me6MPR and formycin to inhibit the growth of the EAC-R2 tumor.

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