scholarly journals Differential cytotoxicity of daunomycin in tumour cells is related to glutathione-dependent hydrogen peroxide metabolism

1981 ◽  
Vol 194 (1) ◽  
pp. 369-372 ◽  
Author(s):  
Argante Bozzi ◽  
Irene Mavelli ◽  
Bruno Mondovi ◽  
Roberto Strom ◽  
Giuseppe Rotilio

Addition of 0.5mm-daunomycin, a quinone anti-cancer drug, causes severe inhibition of respiration in Ehrlich ascites cells, whereas Yoshida ascites cells were almost as resistant as rat hepatocytes. An inverse relationship appears to exist in the two types of tumour cells (which are both catalase-deficient) between the extent of cellular damage brought about by intracellular formation of superoxide anion occurring on reaction with O2 of the drug free radical and the efficiency of the glutathione-mediated H2O2-detoxifying system.

1959 ◽  
Vol 12 (6) ◽  
pp. 473-478 ◽  
Author(s):  
KOUICHI TAKANO ◽  
MASA-ATSU YAMADA ◽  
YASUKO HIROKAWA ◽  
DEN'ICHI MIZUNO ◽  
MIHOKO ABE ◽  
...  

1978 ◽  
Vol 29 (1) ◽  
pp. 271-275
Author(s):  
D.E. Maslow ◽  
L. Weiss

The presence of small numbers of tumour cells inhibits the aggregation of embryonic chicken neural retina cells grown in gyratory shaker culture. The aggregation of neural retina cells was also inhibited by ascites cell medium. We investigated whether the inhibitory effect of the tumour cells on aggregate size is effected by inhibition of the initial adhesion or by enhancement of their separation. The number of neural retina cells adherent to microtest plate surfaces was significantly reduced after incubation with either Ehrlich ascites cells or cell-free, conditioned medium, while the percentage of cells removed from glass by shearing was unchanged under those conditions. These results suggest that the reduction in neural retina cell aggregate size produced by Ehrlich ascites cells and their products is due to partial inhibition of neural retina cell adhesion processes, as distinct from enhancement of separation.


1980 ◽  
Vol 188 (2) ◽  
pp. 491-501 ◽  
Author(s):  
L Alhonen-Hongisto ◽  
H Pösö ◽  
J Jänne

The anti-proliferative effects of 1,1′-[(methylethanediylidene)dinitrilo]diguanidine [methylglyoxal bis(guanylhydrazone)] and 1,1′-[(metHYLETHANEDIYLIDENE)dinitrilo]bis-(3-aminoguaNIDINE) HAVE BEEN STUDIED IN Ehrlich ascites carcinoma cells grown in suspension cultures. Both compounds are potent inhibitors of S-adenosyl-L-methionine decarboxylase from the tumour cells. In the presence of putrescine (but not in its absence), the inhibition produced by 1,1′-[methylethanediylidene)dinitrilo]bis-(3-aminoguanadine) was apparently irreversible, as judged by persistent depression of the enzyme activity even after extensive dialysis. The two compounds produced similar increases in adenosylmethionine decarboxylase activity, which resulted from a striking stabilization of the enzyme in cells grown in the presence of the drugs. The inhibitory effect of the two diguanidine derivatives on the synthesis of DNA and protein became evident after an exposure of 4–8 h. At that time, the only change seen in tumour polyamines in cells grown in the presence of the inhibitors was an increase in cellular putrescine. To find out whether the compounds initially interfered with the energy production of the tumour cells, the cultures were grown in the presence of uniformly labelled glucose, and the formation of lactate, as well as the oxidation of the sugar into CO2, were measured. The activation of glycolysis upon dilution of the tumour cells with fresh medium and the subsequent formation of labelled CO2 were siliar in control cells and in cells exposed to methylglyoxal bis(buanylhydrazone), 1,1′-[(methylethanediylidene)dinitrilo]bis-(3-aminoguanidine) or diaminopropanol. Only a marginal decrease in the cellular content of ATP was found in cells exposed to the inhibitors for 24 h. The diguanidine-induced growth inhibition was fully reversed by low concentrations of exogenous polyamines. However, the possibility remained that the reversal by polyamines was due to a decrease of intracellular diguanidine concentration. Our results indicate that the mode of action of 1,1′-[(methylethanediylidene)dinitrilo]bis-(3-aminoguanidine) is fully comparable to that of methylglyoxal bis(guanylhydrazone), as regards stabilization of adenosylmethionine decarboxylase and the appearance of growth inhibition in Ehrlich ascites cells. The data tend to support the view that both compounds apparently have an early anti-proliferative effect unrelated to polyamine metabolism.


Micromachines ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 681
Author(s):  
Xiaoli Liu ◽  
Huichao Lin ◽  
Jiaao Song ◽  
Taiyi Zhang ◽  
Xiaoying Wang ◽  
...  

Cell culture is important for the rapid screening of anti-cancer drug candidates, attracting intense interest. Traditional 2D cell culture has been widely utilized in cancer biological research. However, 3D cellular spheroids are able to recapitulate the in vivo microenvironment of tissues or tumors. Thus far, several 3D cell culture methods have been developed, for instance, the hanging drop method, spinner flasks and micropatterned plates. Nevertheless, these methods have been reported to have some disadvantages, for example, medium replacement is inconvenient or causes cellular damage. Here, we report on an easy-to-operate and useful micro-hole culture chip (SimpleDrop) for 3D cellular spheroid formation and culture and drug analysis, which has advantages over the traditional method in terms of its ease of operation, lack of shear force and environmentally friendliness. On this chip, we observed the formation of a 3D spheroid clearly. Three drugs (paclitaxel, cisplatin and methotrexate) were tested by both cell viability assay and drug-induced apoptotic assay. The results show that the three drugs present a similar conclusion: cell viability decreased over time and concentration. Moreover, the apoptotic experiment showed a similar trend to the live/dead cell assay, in that the fraction of the apoptotic and necrotic cells correlated with the concentration and time. All these results prove that our SimpleDrop method is a useful and easy method for the formation of 3D cellular spheroids, which shows its potential for both cell–cell interaction research, tissue engineering and anticancer drug screening.


Xenobiotica ◽  
2009 ◽  
Vol 00 (00) ◽  
pp. 090901052053001-8
Author(s):  
K. Murai ◽  
H. Yamazaki ◽  
K. Nakagawa ◽  
R. Kawai ◽  
T. Kamataki

2010 ◽  
Author(s):  
N. Magnavita ◽  
I. lavicoli ◽  
V. Leso ◽  
A. Bergamaschi

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