Wyniki wyszukiwania - Biblioteka Nauki

1

Cytotoxicity and inhibitory properties against topoisomerase II of doxorubicin and its formamidine derivatives

100%

Kik K. , Studzian K. , Wąsowska-Łukawska M. , Oszczapowicz I. , Szmigiero L.

Acta Biochimica Polonica

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2009

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tom 56

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nr 1

135-142

EN

This work was undertaken to compare cytotoxicity, DNA damaging properties and effect on DNA cleavage by topoisomerase II of the anthracycline drug doxorubicin (DOX) and its two derivatives with a formamidino group containing a cyclic amine moiety such as morpholine (DOXM) or hexamethyleneimine (DOXH). The tetrazolium dye colorimetric assay was used to determine the cytotoxic activity of anthracyclines toward L1210 leukemia cells. DNA damage was measured by alkaline elution technique. The effect of anthracyclines on DNA cleavage was studied in a cell-free system containing supercoiled pBR322 DNA and purified human topoisomerase II. The cytotoxicity data and the results of studies on the mechanism of DNA break formation by anthracyclines at the cellular level and in the cell-free system showed that the presence of the formamidino group in the doxorubicin molecule reduced its ability to stimulate DNA cleavage by DNA topoisomerase II. Conclusion: DNA topoisomerase II is not a primary cellular target for DOXM or DOXH. An advantageous feature of formamidinoanthracyclines is their mechanism of cytotoxic action which is not related to the inhibition of DNA topoisomerase II. Therefore this class of anthracyclines seems to be a good source for selection of an anticancer drug directed toward cancer cells with the developed multidrug resistance attributed to the presence of altered DNA topoisomerase II.

2

Structural domains of plant nuclear DNA as a constitutive component of the topoisomerase II-DNA complex

88%

Solovyan V. T. , Andreyev I. O.

Acta Biochimica Polonica

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1995

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tom 42

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nr 2

EN

The treatment of agarose embedded plant nuclei by strong protein dénaturants was demonstrated to result in discrete self-fragmentation of intact nuclear DNA. The set of resultant DNA cleavage products involves two main types of DNA fragments sized about 50-100 kb and 300-500 kb, being of the same type in various eukaryotic representatives. The pattern of ordered DNA fragmentation has been shown to be similar both in intact nuclei and in histone-depleted ones thus suggesting that the observed DNA fragments represent preexisting DNA structural domains, corresponding to the higher levels of chromatin folding. The topoisomerase II-speeific poison teniposide (VM-26) has been shown to increase the ordered DNA cleavage while the conditions stimulating the topoisomerase II-mediated reverse reaction lead to the reassociation of the cleaved DNA domains. The data presented suggest that the nuclear DNA structural domains are involved in functioning of the topoisomerase II/DNA complex, the main property of which is its ability to mediate the cleavage/ /reassociation reactions.

3

The effects of topoisomerase II poison [etoposide] and of topoisomerase II inhibitor ICR 193] on somatic and conjugation nuclear divisions in Tetrahymena thermophila

88%

Kaczanowski A. , Domaradzka A. , Kiersnowska M.

Cellular and Molecular Biology Letters

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2002

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tom 07

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nr Suppl.

4

Cytotoxicity and inhibitory properties against topoisomerase II of doxorubicin and its formamidine derivatives

75%

Kik K. , Studzian K. , Wasowska-Lukawska M. , Oszczapowicz I. , Szmigiero L.

Acta Biochimica Polonica

|

2009

|

tom 56

|

nr 1

135-142

EN

This work was undertaken to compare cytotoxicity, DNA damaging properties and effect on DNA cleavage by topoisomerase II of the anthracycline drug doxorubicin (DOX) and its two derivatives with a formamidino group containing a cyclic amine moiety such as morpholine (DOXM) or hexamethyleneimine (DOXH). The tetrazolium dye colorimetric assay was used to determine the cytotoxic activity of anthracyclines toward L1210 leukemia cells. DNA damage was measured by alkaline elution technique. The effect of anthracyclines on DNA cleavage was studied in a cell-free system containing supercoiled pBR322 DNA and purified human topoisomerase II. The cytotoxicity data and the results of studies on the mechanism of DNA break formation by anthracyclines at the cellular level and in the cell-free system showed that the presence of the formamidino group in the doxorubicin molecule reduced its ability to stimulate DNA cleavage by DNA topoisomerase II. Conclusion: DNA topoisomerase II is not a primary cellular target for DOXM or DOXH. An advantageous feature of formamidinoanthracyclines is their mechanism of cytotoxic action which is not related to the inhibition of DNA topoisomerase II. Therefore this class of anthracyclines seems to be a good source for selection of an anticancer drug directed toward cancer cells with the developed multidrug resistance attributed to the presence of altered DNA topoisomerase II.

5

SARs on an 835 kb DNA fragment from the Drosophila genome

63%

Miassod R. , Jullien N.

Acta Biochimica Polonica

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1995

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tom 42

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nr 2

EN

We have investigated the loop organization of a 835 kilobases DNA fragment from the Drosophila genome. This analysis has focused on the perodicity of the distribution of anchoring sequences (SARs) and its relationship to the distribution of A,T-rich regions, transcription units, repeated elements, putative replication origins and topoisomerase II cleavege sites. Altogether, the data support the idea of an active participation of SARs to the structural organization and functioning of this eukaryotic genome.

6

Topoisomerase II as a target for anticancer chemotherapy

63%

Kaufmann S. H. , Hancock R.

Acta Biochimica Polonica

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1995

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tom 42

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nr 4

EN

Type II DNA topoisomerases are required for the segregation of genomic DNA at cell division in prokaryotic and eukaryotic cells, and inhibitors of these enzymes are potential cytotoxic agents in both prokaryotes and eukaryotes. The bacterial member of the topoisomerase II family, DNA gyrase, and the chemotherapeutic agents which target it are the subject of a recent review (Maxwell, A. et al., 1993, in Molecular Biology of DNA Topoisomerases, Andoh, T. et al., eds.,pp. 21-30, CRC Press, Boca Raton). Here we present an overview of current knowledge of eukaryotic topoisomerase II and the anticancer agents which target this enzyme, focussing predominantly on new observations and recent reports and reviews.

7

DFF40-CAD hypersensitive sites are potentially involved in high molecular weight DNA fragmentation during apoptosis

63%

Widlak P.

Cellular and Molecular Biology Letters

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2000

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tom 05

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nr 3

EN

Sequential cleavage of genomic DNA into large-scale DNA fragments of 50-300-kb, followed by formation of mono- and oligonucleosomal DNA fragments, is a biochemical hallmark of programmed, cell death (apoptosis). The endonuclease DFF40/CAD mediates regulated internucleosomal DNA fragmentation and chromatin condensation in cells undergoing apoptosis. DFF40 hypersensitive sites were detected in purified HeLa cell nuclei, and excision of 50-kb DNA fragments preceded formation of oligonucleosomal DNA ladders in nuclei treated with the nuclease. Topoisomerase II, but not topoisomerase I, stimulates DFF40 activity on plasmid DNA substrates. This suggests that interactions of DFF with the nuclear matrix-bound topoisomerase II may be involved in formation of DFF40 hypersensitive sites.

8

L-proline analogues of anthraquinone-2-carboxylic acid as prolidase-activated prodrugs: cytotoxic activity in breast cancer MCF-7 cells and inhibitory activity against topoisomerase I and II

63%

Bielawska A. , Bielawski K. , Palka J. , Kosk K.

Folia Histochemica et Cytobiologica. Supplement

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2001

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tom 39

|

nr 1

9

Interactions of Drosophila melanogaster lamin Dm with nucleic acids and topoisomerase II in vivo

63%

Rzepecki R. , Fisher P. A.

Cellular and Molecular Biology Letters

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2000

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tom 05

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nr 2

10

Rola apoptozy w fizjologii i patologii komorki

32%

Adamczyk M. , Kostka G. , Palut D.

Roczniki Państwowego Zakładu Higieny

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1998

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tom 49

|

nr 4

415-432

PL

Na podstawie piśmiennictwa omówiono zagadnienia dotyczące śmierci komórkowej, a zwłaszcza apoptozy i jej genetycznych uwarunkowań oraz rolę tego procesu w stanach fizjologicznych i patologicznych komórki.

EN

The cell death is a natural physiological process that occurs in every living organism. It is clear that programmed cell death - apoptosis - is an important mechanism maintaining cell number in a multicellular organism. This review summarises recent progress in the field of apoptosis. Extracellular signals, such as various growth factors and antigene Fas ligand can trigger apoptosis via cell surface receptors. Within the cell the tumor supressor gene p53 and oncogenes c-myc, c-fos and c-jun tend to activate apoptosis, while other genes such as most members of the bcl-2 family, tend to supress it. Many of these signals regulate a family of cysteine proteases - related to interleukine lß converting enzyme (ICE) - caspases - which play a crucial role in apoptosis. Many factors that affect apoptosis also affect the cell cycle. For example, p53 appears to be an important mediator of both apoptosis and cycle arrest. If DNA damage is repaired during cycle arrest, the cell survives. Special attention is paid to the abnormalities in the regulation of apoptosis that may contribute to different pathogenic processes.