4.7 Article

Doxorubicin-induced senescence through NF-κB affected by the age of mouse mesenchymal stem cells

期刊

JOURNAL OF CELLULAR PHYSIOLOGY
卷 235, 期 3, 页码 2336-2349

出版社

WILEY
DOI: 10.1002/jcp.29140

关键词

cell senescence; doxorubicin kinetic model; mesenchymal stem cells; NF-kappa B; telomere length

资金

  1. Iran National Science Foundation
  2. Toxicology and Animal Poisoning Research Center, University of Tehran (Iran)

向作者/读者索取更多资源

The senescence is proposed as a defense mechanism against many anticancer drugs. This complication is marked by differences in cell appearance and inner structures underlying the impairment in function. In this experiment, doxorubicin-induced senescence was assessed in mesenchymal stem cells (MSCs) isolated from the bone marrow of different-aged Balb/c mice (1, 8, and 16 months old). In addition, doxorubicin kinetics in culture medium were investigated to compare the drug absorption rate by different-aged MSCs. Several methods were exerted including Sandwich ELISA for NF-kappa B activation, propidium iodide staining for cell cycle analysis, Flow-fluorescent in-situ hybridization (Flow-FISH) assay for telomere length measurement, and specific staining for evaluation of beta-galactosidase. Determination of doxorubicin in a medium was performed by high-performance liquid chromatography technique. Following doxorubicin exposure, cells underwent substantial telomere shortening, cell cycle arresting in G2 phase, and increased beta-galactosidase activity. Interestingly, the enhanced level of NF-kappa B was observed in all age groups. The highest and lowest sensitivity to telomere shortening attributed to 1- and 8-month-old MSCs, respectively. In consistent with Flow-FISH results, the beta-galactosidase activity was higher in young-aged MSCs after treatment. Statistical analysis indicated a correlation between the reduction of telomere length and cessation in G2 phase. Regarding the obtained kinetics equations, the rate of doxorubicin absorption by all aged MSCs followed the same trend. In conclusion, the changing of some elements involved in doxorubicin-induced senescence can be affected by the age of the cells significantly in young MSCs than two other age groups. Hereupon, these changing patterns can open new insights to develop anticancer therapeutic strategies.

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