Evaluation of a strategy for tumor-initiating stem cell eradication in primary human glioblastoma cultures as a model

E. V. Dolgova, A. S. Proskurina, E. A. Potter, T. V. Tyrinova, O. S. Taranov, Ya R. Efremov, K. E. Orishchenko, S. V. Mishinov, V. V. Stupak, A. A. Ostanin, E. R. Chernykh, S. S. Bogachev

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1 Citation (Scopus)


Primary cultures of human glioblastoma were obtained from the surgical material of patients K. (female, 61 years, Ds: relapse of glioblastoma) and Zh. (female, 60 years, Ds: relapse of glioblastoma). The effectiveness of a new therapeutic approach aimed at destroying the cancer cell community was evaluated on the primary cell lines of human glioblastoma culture by employing a new strategy of tumor-initiating stem cell synchronization and a domestic strategy of their eradication “3+1”. The key elements of the strategy were the following indicator results: (1) evaluation of the presence of tumor-initiating stem cells in a population of cells from analyzed cultures by their ability to internalize double-stranded labeled DNA (TAMRA+ cells); (2) determination of the reference time points of the repair cycle of DNA interstrand cross-links induced by cross-linking cytostatic mitomycin C; (3) evaluation of cell cycle synchronization; (4) determination of the time (day after therapy initiation) when TAMRA+ cells were synchronously present in phase G1/S of the cell cycle, sensitive to the therapy; and (5) establishment of the TAMRA+ (tumor-initiating stem cells) eradication schedule. The cultures were treated with cross-linking cytostatic mitomycin C and a compositional DNA preparation. After the treatments, cell division slows down, and the cultures degrade. The K cell line completely degraded within 30 days of observation. The cell number of the Zh culture fell to nearly one-third of the starting value by day 15 of observation. on day 15, this indicator constituted 1/7.45 for mitomycin C and 1/10.28 for mitomycin C + DNA with reference to the control. The main target of the mitomycin C + DNA regimen was TAMRA+ tumor-initiating stem cells of the glioblastoma cell populations. The action of mitomycin C alone or in the combination with DNA demonstrated effective elimination of TAMRA+ tumor-initiating stem cells and the whole primary cultures of human glioblastomas.

Original languageEnglish
Pages (from-to)825-836
Number of pages12
JournalВавиловский журнал генетики и селекции
Issue number7
Publication statusPublished - 1 Jan 2018


  • Glioblastoma
  • Mytomycin C
  • Primary cell line
  • TAMRA-fluorochrom
  • Tumor-initiating stem cells




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