scholarly journals Inhibiting Apoptosis of CTLL-2 Cells to Enhance their GVL Effects via Anti-Fas Ribozyme

2004 ◽  
Vol 36 (8) ◽  
pp. 559-565
Author(s):  
Min Zhang ◽  
Fang Liu ◽  
Lin-Bo Liu ◽  
Yong You ◽  
Zhi-Chao Chen ◽  
...  

Abstract To investigate the inhibition role of anti-Fas hammerhead ribozyme on fas expression and Fas-mediated apoptosis of CTL cell line CTLL-2 cells, the cDNA of an anti-Fas hammerhead ribozyme was synthesized, its expression plasmid was constructed and transfected into CTLL-2 cells by electroporation. fas expression of CTLL-2 cells was detected by RT-PCR and Western blot. CTLL-2 cell viability was measured using MTT assay when co-cultured with mouse T cell leukemia cell line EL4 cells that highly expressed Fas ligand (FasL). Meanwhile, caspase-3 proteolytic activity was detected, and cell apoptosis was measured by flow cytometry and Hochest-PI double staining. Killing activity of CTLL-2 cells was detected by lactate dehydrogenase (LDH) releasing assay in vitro. Results showed that the expression of both Fas mRNA and protein in CTLL-2 cells were decreased after transfection of anti-Fas ribozyme. Compared with mocktransfected group and mutant ribozyme-transfected group, viability of CTLL-2 cells co-cultured with EL4 cells was increased significantly and cells killing activity was enhanced after transfected with anti-Fas ribozyme, while the caspase-3 activity and apoptosis rate was significantly decreased. The results demonstrated anti-Fas ribozyme could efficiently cleave Fas and inhibit Fas-mediated apoptosis of CTLL-2 cells to improve their viability. Our study made a basis for enhancing CTLL-2 cells anti-leukemia effect in DLI.

1993 ◽  
Vol 79 (6) ◽  
pp. 433-438 ◽  
Author(s):  
Pratima Sur ◽  
Yoshinobu Matsuo ◽  
Takeshi Otanl ◽  
Jun Minowada

In an In vitro study using a human monocytic leukemia cell line, U-937, the effects of interferon-γ (IFN-γ) in combination with the antifolate methotrexate and the role of thymidine introduced as a biochemical modulator were investigated. Methotrexate alone or in combination with INF-γ was found to enhance the induction of morphologic and functional monocytic differentiation in the U-937 cell line. Various cellular effects with the addition of thymidine to the medium with methotrexate and IFN-γ were studied. Enhanced inhibition of cell growth and perturbation of the cell cycle were noted when methotrexate and IFN-γ were used in combination, but not when methotrexate was used alone. The reduction of cellular folate by methotrexate was also enhanced in combination with IFN-γ. Cell cycle delay, resulting in cell growth inhibition of folate depletion, caused the induction of differentiation in U-937 cells, which was found to be greater with methotrexate + IFN-γ than with methotrexate alone. Cellular differentiation, as assessed by nitroblue tetrazolium reduction assay, indirect immunofluorescence and morphology, showed better effects towards the differentiation of U-937 cells when the agents were used in combination. However, addition of thymidine to the medium was found to cancel all the aforementioned effects. The addition of thymidine to the medium also caused reversal of the inhibitory effect of methotrexate and IFN-γ on cell growth and repletion of the endogenous folate level. Repletion of the folate level by exogenous thymidine is a new possibility for the role of the thymidine in cellular growth.


1996 ◽  
Vol 24 (4) ◽  
pp. 581-587
Author(s):  
Cristiana Zanetti ◽  
Arrnalaura Stammati ◽  
Orazio Sapora ◽  
Flavia Zucco

The aim of this study was to investigate the endpoints related to cell death, either necrosis or apoptosis, induced by four chemicals in the promyelocytic leukemia cell line, HL-60. Cell morphology, DNA fragmentation, cytofluorimetric analysis and oxygen consumption were used to classify the type of cell death observed. In our analysis, we found that not all the selected parameters reproduced the differences observed in the cell death caused by the four chemicals tested. As cell death is a very complex phenomenon, several factors should be taken into account (cell type, exposure time and chemical concentration), if chemicals are to be classified according to differences in the mechanisms more directly involved in cell death.


1990 ◽  
Vol 81 (5) ◽  
pp. 449-453 ◽  
Author(s):  
Terutaka Sagawa ◽  
Takeshi Kodama ◽  
Akio Tominaga ◽  
Mariko Okada

Leukemia ◽  
2000 ◽  
Vol 14 (2) ◽  
pp. 299-306 ◽  
Author(s):  
Y Nomura ◽  
O Inanami ◽  
K Takahashi ◽  
A Matsuda ◽  
M Kuwabara

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (02) ◽  
pp. 20-28
Author(s):  
P. K. N. Sarangi ◽  
◽  
J. Sahoo ◽  
S. K Paidesetty ◽  
G. P. Mohanta

A series of several diazenyl Schiff base derivatives were designed and synthesized through azo coupling of diazotised primary amines with the novel synthesized Schiff base ligand (E)-N-((2-chloroquinolin-3-yl) methylene)-4-phenylthiazol-2-amine. All the synthesized compounds have been analysed by different spectral techniques such as elemental analysis, 1H NMR, FT-IR, UV-Vis and LC-MS for their structural confirmation. The above conjugates have been studied for their solvent effects by treating them with different solvents. The results of in vitro cytotoxic study of the synthesized compounds against MCF 7 (human breast cancer cell line) and K562 (Chronic Myeloid Leukemia cell line) revealed that some of the compounds show cytotoxic effect. However, the compounds (NZ)-N-(((4-bromo-3-methylphenyl) diazenyl) (2-chloroquinolin-3-yl) methylene)-4-phenylthiazol-2-amine: (5d) and 4-(((Z)-(2-chloroquinolin-3- yl)(4-phenylthiazol-2-ylimino)methyl)diazenyl)phenol (5e) showed potent cytotoxic activity in comparison to other compounds against MCF 7. Corroborating the results of anticancer activity, it is found to be observed that the compound 4- (((Z)- (2-chloroquinolin-3-yl) (4-phenylthiazol-2-ylimino)methyl) diazenyl) phenol (5e) showed excellent anticancer activity against MCF 7, which is further justified by the apoptosis study through Annexin V-FITC/PI analysis.


Materials ◽  
2020 ◽  
Vol 13 (10) ◽  
pp. 2393
Author(s):  
Jakub Iwanejko ◽  
Elżbieta Wojaczyńska ◽  
Eliza Turlej ◽  
Magdalena Maciejewska ◽  
Joanna Wietrzyk

In the search for new antitumor agents, aminophosphonic acids and their derivatives based on octahydroquinoxalin-2(1H)-one scaffold were obtained and their cytotoxic properties and a mechanism of action were evaluated. Phosphonic acid and phosphonate moieties increased the antiproliferative activity in comparison to phenolic Mannich bases previously reported. Most of the obtained compounds revealed a strong antiproliferative effect against leukemia cell line (MV-4-11) with simultaneous low cytotoxicity against normal cell line (mouse fibroblasts-BALB/3T3). The most active compound was diphenyl-[(1R,6R)-3-oxo-2,5-diazabicyclo[4.4.0]dec-4-yl]phosphonate. Preliminary evaluation of the mechanism of action showed the proapoptotic effect associated with caspase 3/7 induction.


1990 ◽  
Vol 323 (3) ◽  
pp. 133-140 ◽  
Author(s):  
Herta Reile ◽  
Richard Müller ◽  
Ronald Gust ◽  
Reiner Laske ◽  
Walter Krischke ◽  
...  

2004 ◽  
Vol 42 (11) ◽  
pp. 1777-1784 ◽  
Author(s):  
Jen-Hung Yang ◽  
Chi-Chung Chou ◽  
Ya-Wen Cheng ◽  
Lee-Yan Sheen ◽  
Ming-Chi Chou ◽  
...  

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