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Cancer Cell International
Published in: Cancer Cell International 1/2015

Open Access 01-12-2015 | Primary research

Combination of cyclophosphamide and double-stranded DNA demonstrates synergistic toxicity against established xenografts

Authors: Ekaterina A Alyamkina, Valeriy P Nikolin, Nelly A Popova, Alexandra M Minkevich, Artem V Kozel, Evgenia V Dolgova, Yaroslav R Efremov, Sergey I Bayborodin, Oleg M Andrushkevich, Oleg S Taranov, Vladimir V Omigov, Vladimir A Rogachev, Anastasia S Proskurina, Evgeniy I Vereschagin, Elena V Kiseleva, Maria V Zhukova, Alexandr A Ostanin, Elena R Chernykh, Sergey S Bogachev, Mikhail A Shurdov

Published in: Cancer Cell International | Issue 1/2015

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Abstract

Background

Extracellular double-stranded DNA participates in various processes in an organism. Here we report the suppressive effects of fragmented human double-stranded DNA along or in combination with cyclophosphamide on solid and ascites grafts of mouse Krebs-2 tumor cells and DNA preparation on human breast adenocarcinoma cell line MCF-7.

Methods

Apoptosis and necrosis were assayed by electrophoretic analysis (DNA nucleosomal fragmentation) and by measurements of LDH levels in ascitic fluid, respectively. DNA internalization into MCF-7 was analyzed by flow cytometry and fluorescence microscopy.

Results

Direct cytotoxic activity of double-stranded DNA (along or in combination with cyclophosphamide) on a solid transplant was demonstrated. This resulted in delayed solid tumor proliferation and partial tumor lysis due to necrosis of the tumor and adjacent tissues. In the case of ascites form of tumor, extensive apoptosis and secondary necrosis were observed. Similarly, MCF-7 cells showed induction of massive apoptosis (up to 45%) as a result of treatments with double-stranded DNA preparation.

Conclusions

Double-stranded DNA (along or in combination with cyclophosphamide) induces massive apoptosis of Krebs-2 ascite cells and MCF-7 cell line (DNA only). In treated mice it reduces the integrity of gut wall cells and contributes to the development of systemic inflammatory reaction.
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Metadata
Title
Combination of cyclophosphamide and double-stranded DNA demonstrates synergistic toxicity against established xenografts
Authors
Ekaterina A Alyamkina
Valeriy P Nikolin
Nelly A Popova
Alexandra M Minkevich
Artem V Kozel
Evgenia V Dolgova
Yaroslav R Efremov
Sergey I Bayborodin
Oleg M Andrushkevich
Oleg S Taranov
Vladimir V Omigov
Vladimir A Rogachev
Anastasia S Proskurina
Evgeniy I Vereschagin
Elena V Kiseleva
Maria V Zhukova
Alexandr A Ostanin
Elena R Chernykh
Sergey S Bogachev
Mikhail A Shurdov
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2015
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-015-0180-6

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