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

Ekaterina A Alyamkina1, Valeriy P Nikolin1, Nelly A Popova2

  • 1Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia.

Abstract

Insights

Fragmented double-stranded DNA, alone or with cyclophosphamide, demonstrated cytotoxic effects on mouse Krebs-2 tumors and human MCF-7 cells. This treatment induced significant apoptosis and necrosis, impacting tumor growth and cell viability.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Immunology

Background:

  • Extracellular double-stranded DNA plays diverse roles in biological systems.
  • Investigating the therapeutic potential of DNA in cancer treatment is an emerging area.

Purpose of the Study:

  • To evaluate the suppressive effects of fragmented human double-stranded DNA (dsDNA) on solid and ascites forms of mouse Krebs-2 tumor cells.
  • To assess the impact of dsDNA on the human breast adenocarcinoma cell line MCF-7.
  • To examine the combined effects of dsDNA and cyclophosphamide on tumor cells.

Main Methods:

  • Assessing apoptosis via DNA nucleosomal fragmentation and necrosis through LDH levels.
  • Analyzing DNA internalization in MCF-7 cells using flow cytometry and fluorescence microscopy.
  • Treating solid and ascites Krebs-2 tumors and MCF-7 cells with dsDNA and/or cyclophosphamide.

Main Results:

  • Direct cytotoxic activity of dsDNA, with or without cyclophosphamide, was observed against solid tumors, leading to delayed proliferation and partial lysis.
  • Ascites tumors exhibited extensive apoptosis and secondary necrosis following dsDNA treatment.
  • MCF-7 cells showed a significant induction of apoptosis (up to 45%) upon treatment with dsDNA preparation.

Conclusions:

  • Double-stranded DNA, alone or combined with cyclophosphamide, effectively induces massive apoptosis in Krebs-2 ascites cells and MCF-7 cells.
  • In vivo, dsDNA treatment reduced the integrity of gut wall cells, contributing to a systemic inflammatory response.

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