Combination of cyclophosphamide and double-stranded DNA demonstrates synergistic toxicity against established xenografts
| Autor: | Oleg M Andrushkevich, Sergey S. Bogachev, O. S. Taranov, Evgenia V. Dolgova, Maria V Zhukova, Vladimir A. Rogachev, Evgeniy I Vereschagin, Alexandra M. Minkevich, Valeriy P. Nikolin, Elena Kiseleva, Alexandr A. Ostanin, Ekaterina A. Alyamkina, Anastasia S. Proskurina, Nelly A. Popova, Elena R. Chernykh, Mikhail A. Shurdov, Yaroslav R. Efremov, Omigov Vv, Artem V Kozel, Sergey I. Bayborodin |
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| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Necrosis Lysis Apoptosis Double-stranded DNA Flow cytometry chemistry.chemical_compound Ascites Krebs-2 Sepsis Genetics medicine Cytotoxic T cell Fragmentation (cell biology) Cyclophosphamide medicine.diagnostic_test business.industry Molecular biology Oncology chemistry Cell culture Immunology MCF-7 medicine.symptom Primary Research business DNA |
| Zdroj: | Cancer Cell International |
| ISSN: | 1475-2867 |
| DOI: | 10.1186/s12935-015-0180-6 |
| Popis: | 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. Electronic supplementary material The online version of this article (doi:10.1186/s12935-015-0180-6) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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