scholarly journals Inducible Protective Processes in Animal Systems XIII: Comparative Analysis of Induction of Adaptive Response by EMS and MMS in Ehrlich Ascites Carcinoma Cells

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Periyapatna Vishwaprakash Mahadimane ◽  
Venkateshaiah Vasudev

In order to investigate the presence of adaptive response in cancerous cells, two monofunctional alkylating agents, namely, ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS), were employed to treat Ehrlich ascites carcinoma (EAC) cellsin vivo. Conditioning dose of 80 mg/kg body weight of EMS or 50 mg/kg body weight of MMS and challenging dose of 240 mg/kg body weight of EMS or 150 mg/kg body weight of MMS were selected by pilot toxicity studies. Conditioned EAC cells when challenged after 8 h time lag resulted in significant reduction in chromosomal aberrations compared to challenging dose of respective agents. As has been proved in earlier studies with normal organisms, even in cancerous cells (EAC), there is presence of adaptive response to methylating and ethylating agents. Furthermore, it is also interesting to note in the present studies that the methylating agent, MMS, is a stronger inducer of the adaptive response than the ethylating agent, EMS.

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

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.


Author(s):  
Masnoon Kabir ◽  
Abdullah AL-Noman ◽  
Biplab Kumar Dash ◽  
Mahmudul Hasan ◽  
Shahina Akhter ◽  
...  

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.


2019 ◽  
Vol 35 (1) ◽  
pp. 79-81
Author(s):  
Md Jakir Hossain ◽  
Shashwata Biswas ◽  
Mohammad Shahriar ◽  
Sohidul Islam ◽  
Chowdhury Rafiqul Ahsan

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


2007 ◽  
Vol 15 (3-4) ◽  
pp. 65-68
Author(s):  
Karmen Stankov ◽  
Katica Bajin-Katic ◽  
Bojan Stanimirov ◽  
Dunja Karadzic ◽  
Zoran Kovacevic

Background: One of the most important strategies in research and development of new anticancer agents is the tumor-specific induction of apoptosis. The effects of semisynthetic derivative of vitamin E, (?-TOS, D-?-tocopheryl succinate), appear to be largely restricted to malignant cells. Methods: We investigated the in vivo effects of intraperitoneally administered ?-TOS on vitality of Ehrlich ascites carcinoma cells (EAC) in mice, as well as the influence of ?-TOS on specific activity of enzymes involved in antioxidative mechanisms in EAC cells. Results: According to our results, the intraperitoneal application of ?-TOS induces the decrease of the EAC vitality, and the statistically significant alteration of the glutathione-dependent enzyme activity in EAC cells. Conclusion: We may conclude that ?-TOS is an important micronutrient, with significant impact on vitality and metabolism of malignant cells.


2010 ◽  
Vol 3 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Sujata Maiti Choudhury ◽  
Malaya Gupta ◽  
Upal Kanti Majumder

Many fungal toxins exhibit in vitro and in vivo antineoplastic effects on various cancer cell types. Luteoskyrin, a hydroxyanthraquinone has been proved to be a potent inhibitor against Ehrlich ascites tumor cells. The comparative antitumor activity and antioxidant status of MT81 and its structural analogue [Acetic acid-MT81 (Aa-MT81)] having polyhydroxyanthraquinone structure were assessed against Ehrlich ascites carcinoma (EAC ) tumor in mice. The in vitro cytotoxicity was measured by the viability of EAC cells after direct treatment of the said compounds. In in vivo study, MT81 and its structural analogue were administered (i.p.) at the two different doses (5, 7 mg MT81; 8.93, 11.48 mg Aa-MT81/kg body weight) for 7 days after 24 hrs. of tumor inoculation. The activities were assessed using mean survival time (MST), increased life span (ILS), tumor volume, viable tumor cell count, peritoneal cell count, protein percentage and hematological parameters. Antioxidant status was determined by malondialdehyde (MDA) and reduced glutathione (GSH ) content, and by the activity of superoxide dismutase (SOD) and catalase (CA T). MT81 and its structural analogues increased the mean survival time, normal peritoneal cell count. They decreased the tumor volume, viable tumor cell count, hemoglobin percentage and packed cell volume. Differential counts of WBC, total counts of RBC & WBC that altered by EAC inoculation, were restored in a dose-dependent manner. Increased MDA and decreased GSH content and reduced activity of SOD, and catalase in EAC bearing mice were returned towards normal after the treatment of MT81 and its structural analogue. Being less toxic than parent toxin MT81, the structural analogue showed more prominent antineoplastic activities against EAC cells compared to MT81. At the same time, both compounds exhibit to some extent antioxidant potential for the EAC-bearing mice.


Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 502 ◽  
Author(s):  
Imtiaj Hasan ◽  
A.K.M. Asaduzzaman ◽  
Rubaiya Rafique Swarna ◽  
Yuki Fujii ◽  
Yasuhiro Ozeki ◽  
...  

MytiLec-1, a 17 kDa lectin with β-trefoil folding that was isolated from the Mediterranean mussel (Mytilus galloprovincialis) bound to the disaccharide melibiose, Galα(1,6) Glc, and the trisaccharide globotriose, Galα(1,4) Galβ(1,4) Glc. Toxicity of the lectin was found to be low with an LC50 value of 384.53 μg/mL, determined using the Artemia nauplii lethality assay. A fluorescence assay was carried out to evaluate the glycan-dependent binding of MytiLec-1 to Artemia nauplii. The lectin strongly agglutinated Ehrlich ascites carcinoma (EAC) cells cultured in vivo in Swiss albino mice. When injected intraperitoneally to the mice at doses of 1.0 mg/kg/day and 2.0 mg/kg/day for five consecutive days, MytiLec-1 inhibited 27.62% and 48.57% of cancer cell growth, respectively. Antiproliferative activity of the lectin against U937 and HeLa cells was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro in RPMI-1640 medium. MytiLec-1 internalized into U937 cells and 50 μg/mL of the lectin inhibited their growth of to 62.70% whereas 53.59% cell growth inhibition was observed against EAC cells when incubated for 24 h. Cell morphological study and expression of apoptosis-related genes (p53, Bax, Bcl-X, and NF-κB) showed that the lectin possibly triggered apoptosis in these cells.


2020 ◽  
Vol 7 (11) ◽  
pp. 4100-4113
Author(s):  
Hamed A. Abosharaf ◽  
Mohammed Salah ◽  
Thoria Diab ◽  
Motonari Tsubaki ◽  
Tarek M. Mohamed

Introduction: Plant-mediated synthesis of silver nanoparticles (AgNPs) is accounted as an ecofriendly process. The present study was conducted to estimate the potency of biogenic AgNPs against Ehrlich ascites carcinoma (EAC) cells in vitro and EAC-bearing mice in vivo. Methods: AgNPs were prepared using mango leaves extract and characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscopy (TEM). Ehrlich ascites carcinoma (EAC) mouse model was established by intraperitoneal injection of 1 x 106 EAC cells. Biogenic AgNPs- alone or combined with Doxorubicin (DOX)- was administered intraperitoneally day by day for two weeks. Results: Biologically synthesized AgNPs showed a cytotoxic effect against cultured EAC cells but with less toxicity toward normal cells compared to DOX, which had strong cytotoxicity against both cells. Biogenic AgNPs alone or combined with DOX triggered the cytotoxicity against the EAC-bearing mouse model via decreasing body weight, tumor volume, and the number of viable tumor cells. The combined treatment (AgNPs-DOX) ameliorated the drastic effect induced by injection of EAC cells through improving liver and kidney functions compared to those treated with DOX alone. In addition, the combined treatment showed an elevation in the expression of Bax and caspase-3, and a reduction in the expression of Bcl-2 protein in the EAC cells. Furthermore, this combined treatment effectively arrested the cell cycle at the G0/G1 phase. Moreover, the combined treatment with AgNPs-DOX caused a significant reduction in the activity of ornithine decarboxylase (ODC). Conclusion: These findings suggest that biogenic AgNPs could be useful in developing a potent combination therapy against different types of cancers.


2019 ◽  
Vol 09 ◽  
Author(s):  
Ruksana Yesmin ◽  
Plabon Kumar Das ◽  
Hazrat Belal ◽  
Suraiya Aktar ◽  
Ayesha Siddika ◽  
...  

Background: Adverse side effects of currently available therapies against cancer, leads scientists to find effective compounds from natural sources. Objective: In the present study, stem-bark of Mycelia champaca is subjected to evaluate its anti-proliferative effect against Ehrlich ascites carcinoma (EAC) cells. To date, anti-proliferative effects of M. champaca bark extract against EAC cell line has not been reported elsewhere. Therefore, we intended to investigate the anti-proliferative potential of M. champaca bark extract against EAC cells in vivo. Methods: In vivo anticancer activity was evaluated against EAC cells bearing Swiss albino mice by monitoring parameters such as tumor cell proliferation, tumor weight measurement, and survival time etc. The mechanism of EAC killing was examined by observation of cell morphology and analysis the expression of certain cancer related genes. In vitro antioxidant potentiality was determined in terms of several common antioxidant assays. In addition, total phenolic and flavonoids contents were measured to insure the presence of phytochemicals. Results: M. champaca bark extract showed strong antioxidant activities which were found to be strongly correlated (P< 0.001) with phenolics and flavonoids contents. Furthermore, it was found that bark extract decreased tumor cell proliferation (77.46%; P< 0.01), tumor weight (42.13%; P< 0.001) and increased life span of tumor bearing mice (71.97%; P< 0.01) at the dose of 250mg/kg (intraperitoneal; i.p.). M. champaca bark also altered the depleted hematological parameters such as red blood cell, white blood cell, hemoglobin (Hb%) towards normal in tumor bearing mice. In addition, upregulation ofp53, Bax and downregulation Bcl-2 followed by treatmentindicated M. champacabark could induce apoptosis of EAC cells. Conclusion: These results indicated that MEMCB possesses significant cytotoxic activities against EAC cells and has a strong in vitro antioxidant capacity. Therefore, bark of M. champaca could be considered as a potential resource of anti-cancer agents, which might be used to formulate effective anticancer drugs.


Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3313 ◽  
Author(s):  
El-Saied ◽  
El-Aarag ◽  
Salem ◽  
Said ◽  
Khalifa ◽  
...  

The current study aimed to synthesize new metal coordination complexes with potential biomedical applications. Metal complexes were prepared via the reaction of isatin-N(4)anti- pyrinethiosemicarbazone ligand 1 with Cu(II), Ni(II), Co(II), Zn(II), and Fe(III) ions. The obtained metal complexes 2−12 were characterized using elemental, spectral (1H-NMR, EPR, Mass, IR, UV-Vis) and thermal (TGA) techniques, as well as magnetic moment and molar conductance measurements. In addition, their geometries were studied using EPR and UV−Vis spectroscopy. To evaluate the in vivo anti-cancer activities of these complexes, the ligand 1 and its metal complexes 2, 7 and 9 were tested against solid tumors. The solid tumors were induced by subcutaneous (SC) injection of Ehrlich ascites carcinoma (EAC) cells in mice. The impact of the selected complexes on the reduction of tumor volume was determined. Also, the expression levels of vascular endothelial growth factor (VEGF) and cysteine aspartyl-specific protease-7 (caspase-7) in tumor and liver tissues of mice bearing EAC tumor were determined. Moreover, their effects on alanine transaminase (ALT), aspartate transaminase (AST), albumin, and glucose levels were measured. The results revealed that the tested compounds, especially complex 9, reduced tumor volume, inhibited the expression of VEGF, and induced the expression of caspase-7. Additionally, they restored the levels of ALT, AST, albumin, and glucose close to their normal levels. Taken together, our newly synthesized metal complexes are promising anti-cancer agents against solid tumors induced by EAC cells as supported by the inhibition of VEGF and induction of caspase-7.


2021 ◽  
Vol 11 (5) ◽  
pp. 12958-12972

The current study aimed to evaluate the in vitro and in vivo anticancer potential of the silver nanoparticles fabricated with butanol fraction of Pinus roxburghii needles (PNb-AgNPs). In vitro results revealed significant cytotoxicity of PNb-AgNPs towards Ehrlich Ascites Carcinoma (EAC) cells with an IC50 of 47.02 ± 1.11 μg/ml. Further, morphological changes, Reactive Oxygen Species (ROS) generation, mitochondrial depolarization, and DNA fragmentation elucidated EAC cell death by PNb-AgNPs exposure. The cell cycle analysis displayed an increase in the Sub-G1 population (52%), further confirmed by nuclear fragmentation in EAC cells after PNb-AgNPs treatment. The hemolytic investigation revealed the biocompatible nature of PNb-AgNPs. In vivo experiments were performed using the liquid Ehrlich Ascites Carcinoma tumor model, which clearly showed a reduction in tumor growth and body weight following PNb-AgNPs treatment in EAC-bearing mice as compared to untreated controls. Moreover, elevated hematological and biochemical parameters were found to restore to normal range in EAC-bearing mice treated with PNb-AgNPs. Overall, PNb-AgNPs effectively induced apoptotic cell death in EAC cells and exhibited remarkable in vivo antitumor potential.


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