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.

scholarly journals Growth Inhibitory Effects of Ester Derivatives of Menahydroquinone-4, the Reduced Form of Vitamin K2(20), on All-Trans Retinoic Acid-Resistant HL60 Cell Line

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 758
Author(s):  
Hirofumi Yamakawa ◽  
Shuichi Setoguchi ◽  
Shotaro Goto ◽  
Daisuke Watase ◽  
Kazuki Terada ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Adverse Effects ◽  
Vitamin K2 ◽  
Reduced Form ◽  
Inhibitory Effects ◽  
Hl60 Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Growth Inhibitory ◽  
Derivatives Of

The first-choice drug for acute promyelocytic leukemia (APL), all-trans retinoic acid (ATRA), frequently causes drug-resistance and some adverse effects. Thus, an effective and safe agent for ATRA-resistant APL is needed. Menaquinone-4 (MK-4, vitamin K2(20)), used for osteoporosis treatment, does not have serious adverse effects. It has been reported that MK-4 has growth-inhibitory effects on HL60 cells by inducing apoptosis via the activation of Bcl-2 antagonist killer 1 (BAK). However, the effect of MK-4 on ATRA-resistant APL has not been reported. Here, we show that ester derivatives of menahydroquinone-4 (MKH; a reduced form of MK-4), MKH 1,4-bis-N,N-dimethylglycinate (MKH-DMG) and MKH 1,4-bis-hemi-succinate (MKH-SUC), exerted strong growth-inhibitory effects even on ATRA-resistant HL60 (HL-60R) cells compared with ATRA and MK-4. MKH delivery after MKH-SUC treatment was higher than that after MK-4 treatment, and the results indicated apoptosis induced by BAK activation. In contrast, for MKH-DMG, reconversion to MKH was slow and apoptosis was not observed. We suggest that the ester forms, including monoesters of MKH-DMG, exhibit another mechanism independent of apoptosis. In conclusion, the MKH derivatives (MKH-SUC and MKH-DMG) inhibited not only HL60 cells but also HL-60R cells, indicating a potential to overcome ATRA resistance.

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.

scholarly journals Alkaloid-Rich Crude Extracts, Fractions and Piperamide Alkaloids of Piper guineense Possess Promising Antibacterial Effects

Antibiotics ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 98 ◽  
Author(s):  
Eunice Mgbeahuruike ◽  
Pia Fyhrquist ◽  
Heikki Vuorela ◽  
Riitta Julkunen-Tiitto ◽  
Yvonne Holm
Keyword(s):  
Antibacterial Activity ◽  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Hot Water ◽  
Bacterial Strains ◽  
Inhibitory Effects ◽  
Piper Guineense ◽  
E Coli ◽  
Growth Inhibitory ◽  
Derivatives Of

Piper guineense is a food and medicinal plant commonly used to treat infectious diseases in West-African traditional medicine. In a bid to identify new antibacterial compounds due to bacterial resistance to antibiotics, twelve extracts of P. guineense fruits and leaves, obtained by sequential extraction, as well as the piperine and piperlongumine commercial compounds were evaluated for antibacterial activity against human pathogenic bacteria. HPLC-DAD and UHPLC/Q-TOF MS analysis were conducted to characterize and identify the compounds present in the extracts with promising antibacterial activity. The extracts, with the exception of the hot water decoctions and macerations, contained piperamide alkaloids as their main constituents. Piperine, dihydropiperine, piperylin, dihydropiperylin or piperlonguminine, dihydropiperlonguminine, wisanine, dihydrowisanine and derivatives of piperine and piperidine were identified in a hexane extract of the leaf. In addition, some new piperamide alkaloids were identified, such as a piperine and a piperidine alkaloid derivative and two unknown piperamide alkaloids. To the best of our knowledge, there are no piperamides reported in the literature with similar UVλ absorption maxima and masses. A piperamide alkaloid-rich hexane leaf extract recorded the lowest MIC of 19 µg/mL against Sarcina sp. and gave promising growth inhibitory effects against S. aureus and E. aerogenes as well, inhibiting the growth of both bacteria with a MIC of 78 µg/mL. Moreover, this is the first report of the antibacterial activity of P. guineense extracts against Sarcina sp. and E. aerogenes. Marked growth inhibition was also obtained for chloroform extracts of the leaves and fruits against P. aeruginosa with a MIC value of 78 µg/mL. Piperine and piperlongumine were active against E. aerogenes, S. aureus, E. coli, S. enterica, P. mirabilis and B. cereus with MIC values ranging from 39–1250 µg/mL. Notably, the water extracts, which were almost devoid of piperamide alkaloids, were not active against the bacterial strains. Our results demonstrate that P. guineense contains antibacterial alkaloids that could be relevant for the discovery of new natural antibiotics.

scholarly journals Synthesis and Comparative Evaluation of Polymethoxy Substituted 1,4-Naphthoquinones and their Acetyl-O-glucosides as Cytotoxic Agents

2017 ◽  
Vol 12 (7) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Yuri E. Sabutski ◽  
Marina N. Semenova ◽  
Ekaterina A. Yurchenko ◽  
Nikita S. Polonik ◽  
Vladimir A. Denisenko ◽  
...  
Keyword(s):  
Comparative Evaluation ◽  
Ehrlich Ascites Carcinoma ◽  
Carcinoma Cells ◽  
Cytotoxic Agents ◽  
Cytotoxic Effects ◽  
Micromolar Concentration ◽  
Sea Urchin Embryo ◽  
Ehrlich Ascites ◽  
Methoxy Groups ◽  
Derivatives Of

Twenty five hydroxy-, chloro- and methoxy derivatives of natural and synthetic naphthazarins and their acetylated O-glycosides were synthesized. Targeted compounds were screened as cytotoxic agents on mouse Ehrlich ascites carcinoma cells using MTT test. Chloro- and methoxy-substituted naphthoquinones as well as naphthoquinone O-acetylglucosides were the most potent with IC50 in low micromolar concentration range. Glucosidation of hydroxynaphthoquinones was shown to enhance cytotoxicity, whereas methoxylation yielded both more active and less active derivatives depending on the number and position of methoxy groups. Evaluation using a phenotypic sea urchin embryo assay suggested that naphthazarins exerted their cytotoxic effects through tubulin-unrelated mechanism.

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.

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.

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.

BIOCHEMICAL STUDIES ON 1-AMINOCYCLOPENTANE CARBOXYLIC ACID

1962 ◽  
Vol 40 (1) ◽  
pp. 1101-1110 ◽  
Author(s):  
K. Ahmed ◽  
P. G. Scholefield
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Carboxylic Acid ◽  
Brain Cortex ◽  
Ehrlich Ascites Carcinoma ◽  
Carcinoma Cells ◽  
Inhibitory Effects ◽  
Synthetic Amino Acid ◽  
Ehrlich Ascites ◽  
Biochemical Studies

The synthetic amino acid 1-aminocyclopentane carboxylic acid does not seem to be metabolized but is actively concentrated by slices of rat brain cortex and Ehrlich ascites carcinoma cells. Its transport into the ascites cells has much in common with that of methionine since they are both inhibited by similar groups of amino acids. Kinetic analysis of the inhibitory effects of glycine, D- and L-methionine, allyl glycine, and thienyl glycine on the transport of 1-aminocyclopentane carboxylic acid confirms the suggestion that this amino acid and methionine enter ascites cells as the result of the action of a common transport system.

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

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