A New Class of Antimetabolites: Pyridine Thioglycosides as Potential Anticancer Agents

2010 ◽  
Vol 65 (9-10) ◽  
pp. 577-587 ◽  
Author(s):  
Galal H. Elgemeie ◽  
Elsayed M. Mahdy ◽  
Mona A. Elgawish ◽  
Mohammad M. Ahmed ◽  
Wafaa G. Shousha ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Body Weight ◽  
Cytotoxic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Human Cell ◽  
Carcinoma Cell ◽  
Carcinoma Cell Line ◽  
Human Cell Lines ◽  
M Phase

The present study was designed for highlighting and focusing on the cytotoxic activity of a new class of antimetabolites both on human cell lines, namely liver carcinoma cell line (Hepg2), lung carcinoma cell line (H460), breast carcinoma cell line (MCF7), brain carcinoma cell line (U251), and animal cell line EAC (Ehrlich ascites carcinoma cells). The results revealed that some of these modified deazapyrimidine thioglycosides have significant cytotoxic activity against EAC cells with growth inhibition percentage ranged between 80% to 90%. The possible inhibitory mechanism of the pyridine thioglycosides was explored by studying the cell cycle perturbation of thioglycosides against human cell lines (in vitro) as well as the most suitable time for maximum compound cytotoxic activity after 6, 18, and 24 h of incubation. To confirm the cytotoxic activity of these compounds, they have been tested for their apoptotic and antiproliferative activity in vivo against solid Ehrlich tumours using five groups of Swiss albino mice for 37 days from inoculation and three treatments, 250, 500 and 1,000 μg/kg body weight. There was signifi cant reduction in Ehrlich tumour size in case of the 500 and 1,000 μg/kg body weight group but mild significant tumour reduction in the 250 μg/kg body weight group. Histograms of DNA per cell for each treatment group indicated that there was a dose-dependent increase in the preG1 phase with a corresponding complete arrest of cells from entering the G2/M phase compared to the untreated EAC group. In conclusion, pyridine thioglycosides have proven good cytotoxic effects against EAC cells and also significant cytotoxic activity against the four tested human cell lines. Flow cytometric DNA ploidy analysis of pyridine thioglcyosides against the Hepg2 and U251 cell lines revealed that the postulated mechanism of action of pyridine thioglcyosides is cell cycle arrest in the S phase. This is similar to antimetabolites and cell cycle arrest in the G2/M phase (M phase) in the same way as microtubule inhibitors like pyridine thioglycosides are cell-cycle-specific in the S phase and the M phase (in case of human cell lines) and have apoptotic effects (in case of animal cell line).

scholarly journals Effects of quercetin on proliferation and cell cycle of colon carcinoma cell Line HT-29

2006 ◽  
Vol 14 (11) ◽  
pp. 1071
Author(s):  
Xin-Yun Yan ◽  
Jun-Hua Peng ◽  
Hua-Xin Zhang ◽  
Feng Zhang ◽  
Xiao-Hong Bian ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Colon Carcinoma ◽  
Carcinoma Cell ◽  
Carcinoma Cell Line ◽  
Colon Carcinoma Cell Line ◽  
Ht 29

scholarly journals Novel Synthesis Method of Micronized Ti-Zeolite Na-A and Cytotoxic Activity of Its Silver Exchanged Form

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
H. F. Youssef ◽  
W. H. Hegazy ◽  
H. H. Abo-almaged ◽  
G. T. El-Bassyouni
Keyword(s):  
Cytotoxic Activity ◽  
Cell Line ◽  
Carcinoma Cell ◽  
Synthesis Method ◽  
Carcinoma Cell Line ◽  
Breast Adenocarcinoma ◽  
Synthetic Process ◽  
Colon Cell ◽  
Colon Cell Line

The core-shell method is used as a novel synthetic process of micronized Ti-Zeolite Na-A which involves calcination at 700°C of coated Egyptian Kaolin with titanium tetrachloride in acidic medium as the first step. The produced Ti-coated metakaolinite is subjected to microwave irradiation at low temperature of 80°C for 2 h. The prepared micronized Ti-containing Zeolites-A (Ti-Z-A) is characterized by FTIR, XRF, XRD, SEM, and EDS elemental analysis. Ag-exchanged form of Ti-Z-Ag is also prepared and characterized. The Wt% of silver exchanged onto the Ti-Zeolite structure was determined by atomic absorption spectra. Thein vitrocytotoxic activity of Ti-Z-Ag against human hepatocellular carcinoma cell line (HePG2), colon cell line carcinoma (HCT116), lung carcinoma cell line (A549), and human Caucasian breast adenocarcinoma (MCF7) is reported. The results were promising and revealed that the exchanged Ag form of micronized Ti-Zeolite-A can be used as novel antitumor drug.

scholarly journals A clear cancer cell line (150057) derived from human endometrial carcinoma harbors two novel mutations

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yu-Hsun Chang ◽  
Dah-Ching Ding
Keyword(s):  
Endometrial Cancer ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Clear Cell ◽  
Carcinoma Cell ◽  
Clear Cell Carcinoma ◽  
Carcinoma Cell Line ◽  
Novel Mutations

Abstract Background Cell lines are extremely useful for both basic and clinical research. Thus, establishing endometrial cancer cell lines with malignant histology is important. This study aimed to extensively characterize an endometrial clear cell carcinoma cell line. Methods This cell line, named 150,057, was derived from the endometrial clear cell cancer of a 63-year-old woman. The morphology, chromosomes, chemosensitivity, tumor markers, xenotransplantation characteristics, and cancer-related genes of the cell line were characterized. Results This cell line exhibited adequate growth, being passaged more than 70 times. The morphology of the cells was polygonal with a cobblestone-like appearance. Karyotyping of the cell line revealed a hypodiploid chromosomal number. 150057 cells expressed CA19–9 and CA125. The cell line was sensitive to doxorubicin, paclitaxel, carboplatin, and cisplatin. After the cells were transplanted into the subcutaneous region of non-obese diabetic-severe combined immunodeficiency mice, they generated xenograft tumors with similar histology as the original tumor. A total of 59 somatic nucleotide mutations were identified in 25 of the 53 examined tumor suppressor genes and oncogenes. Two novel mutations were found in FGFR3 and ARID1A. Conclusion We established and characterized an endometrial clear cell carcinoma cell line that may be useful in carcinogenesis and treatment research for endometrial cancer.

Physiological Expression of Calr Mutant Increases Cell Growth and Cytokine Independency in Human Cell Lines Expressing Mpl, and Develops Essential Thrombocythemia in Mice

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 954-954
Author(s):  
Kotaro Shide ◽  
Takuro Kameda ◽  
Masaaki Sekine ◽  
Ayako Kamiunten ◽  
Keiichi Akizuki ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cell Line ◽  
Cell Lines ◽  
Human Cell ◽  
Expression Level ◽  
Leukemia Cell Line ◽  
Human Cell Lines ◽  
Gm Csf ◽  
Exon 9 ◽  
Calr Mutation

Abstract Calreticulin (CALR) exon 9 mutations were reported in about two-thirds of JAK2 or MPL mutation negative ET and PMF patients. The mutations cause frameshifts that result in proteins with novel C-terminus.Retrovirus-mediated gene transfer into cell lines and mouse bone marrow (BM) cells is a common technique, but the expression level is very high compared to the physiological expression.We investigated the effects of physiological expression of mutant CALR using CRISPR/Cas9 gene editing techniques for cell lines, and as for the mouse model, we generated a transgenic mice (TG) expressing human CALR del52 mutant. We used two human cell lines expressing MPL: human acute megakaryoblastic leukemia cell line CMK11-5 which expressed endogenous MPL, and F-36P-MPL cell line which was generated by introducing MPL to GM-CSF-dependent erythroleukemia cell line F-36P. Plasmids coexpressing hCas9 and single-guide RNA were prepared by ligating oligonucleotides (5'-CACCGACAAGAAACGCAAAGAGGAGG-3', 5'-AAACCCTCCTCTTTGCGTTTCTTGTC-3') for the target sequence of human CALR exon 9 into pX330. The plasmids were introduced with a electroporator to each of the cell lines. After limiting dilution cloning, we identified cell lines which have indel mutation at the target site. We produced two types of CMK11-5 subline knocked in a CALR mutation, namely CALR del25 CMK cells and CALR del25/del17 CMK cells, respectively. The former lacks 25 bases in one CALR allele, causing a frameshift that results in a protein resembling human CALR mutant, while the latter lacks an additional 17 bases in another allele in CALR exon 9 and induces a frameshift that causes a deletion in CALR exon 9. Both kinds of CALR mutant CMK11-5 cells showed increased cell proliferation compared to WT cells. We also produced one type of F-36P-MPL subline, CALR del1/ins1 F-36P-MPL cells which had 1 base deletion in one CALR allele resembling human mutation and 1 base insertion in another allele. Though the growth of this subline in the presence of GM-CSF was comparable to WT cells, it showed GM-CSF independent autonomous cell growth. We generated TG mice expressing human CALR del52 mutant driven by the murine H2Kb promoter. We compared the expression level of human CALR mRNA in TG BM cells with the expression of endogenous WT CALR in human cell lines (CMK11-5, F-36P-MPL, CHRF288) using Rn18s as an endogenous control. The expression of human CALR in TG BM was approximately 0.6 times that of endogenous WT CALR in human cell lines, and the physiological expression level was obtained. They exhibited thrombocytosis, with platelet (PLT) counts as high as 2,000 x 109/L. Leukocyte number and the proportion of granulocytes and T and B lymphocytes, were comparable to WT mice. CALR mutation had no impact on Hb level or spleen weight. There was a striking difference in the number of megakaryocytes (Mgks), which was 2-fold higher in BM from TG mice than in WT mice. The TG Mgks were also more mature, with larger diameter, and contained higher number of alpha-granules compared to WT cells. In one year of observation, there is no fibrosis in BM. These observations showed that TG developed human ET-like disease. The survival of TG mice was comparable to that of WT mice. The disease phenotype was transplantable into WT recipient mice. To characterize in detail the impact of MPNs induced by the CALR del52 mutant, we evaluated the frequencies of HSCs and progenitors in BM. The frequency of both LT-HSC and ST-HSC in BM was higher inTG mice compared to WT mice. The frequencies of progenitors (CMP, MEP, and MKP) were also greater in BM from TG mice than from WT mice. However, BM cells did not have enhanced replating capacity. We next examined whether or not ruxolitinib (RUX) treatment ameliorated thrombocytosis in TG mice. Either 90 mg/kg bid of RUX or vehicle was administrated to TG mice for 4 weeks.TG mice treated with vehicle showed a mean 16% increase in PLT count during the treatment period, probably due to the disease progression. RUX treatment attenuated the increase in the number of PLTs in TG mice by a mean of 22%, but the overall count was still higher than that in WT mice. BM sections showed that RUX reduced the Mgks number in TG. In summary, physiological expression of CALR mutant increases cell growth and cytokine independency in human cell lines expressing MPL, and develops ET in mice. RUX therapy attenuated the increased numbers of peripheral blood PLTs and BM Mgks, and ameliorated CALR mutation-induced ET. Disclosures No relevant conflicts of interest to declare.

scholarly journals Determination of tissue-type plasminogen-activator mRNA in human and non-human cell lines by dot-blot hybridization

1985 ◽  
Vol 231 (2) ◽  
pp. 309-313 ◽  
Author(s):  
G Opdenakker ◽  
A Billiau ◽  
G Volckaert ◽  
P de Somer
Keyword(s):  
Cell Line ◽  
Plasminogen Activator ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Human Cell ◽  
Melanoma Cell Line ◽  
Tissue Type ◽  
Human Cell Lines ◽  
Dot Blot ◽  
Blot Technique

A labelled cDNA clone was used in DNA-RNA hybridization on nitrocellulose filter paper (dot-blot technique) to detect and quantify mRNA for endogenous tissue plasminogen activator (PA) in cell extracts and samples of RNA purification runs. Although, for detection purposes, the assay was less sensitive than translation in Xenopus oocytes, it was at least as reliable and much more convenient for the purpose of quantitative determination. In particular, the technique was used to study the kinetics of PA mRNA formation in a human melanoma cell line (Bowes) after exposure to the tumour promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Incubation of the cells with TPA resulted in a 15-20-fold increase in cellular PA mRNA content. The effect was time- and dose-dependent: the increase in PA-specific mRNA was clearly visible as early as 4 h after initiation of TPA treatment in Bowes cells. It was blocked completely by pretreatment of the cells with actinomycin D, indicating that TPA caused enhancement of synthesis of PA mRNA rather than inhibition of PA mRNA degradation. The use of the nitrocellulose dot-blot technique also revealed that two non-human cell lines produce mRNAs which cross-react with the human PA mRNA, namely the mouse melanoma cell line B16 and the rat brain-tumour cell line, RT4-71-1. TPA was found to exert similar stimulatory effects on the synthesis of mRNAs in these cell lines as in Bowes cells.

scholarly journals 2-Methoxyestradiol-bis-sulphamate disrupts microtubule network, arrests cell cycle and induces apoptosis in an esophageal carcinoma cell line

2012 ◽  
Vol 31 (1) ◽  
Author(s):  
T.V. Mqoco ◽  
Sumari Marais ◽  
Annie M. Joubert
Keyword(s):  
Cell Cycle ◽  
Esophageal Carcinoma ◽  
Cell Line ◽  
Anticancer Drug ◽  
Carcinoma Cell ◽  
In Vitro Studies ◽  
Carcinoma Cell Line ◽  
Microtubule Network

Future in vitro studies into the mechanism of this potentially anticancer drug are warranted.

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