Details

Autor(en) / Beteiligte

• Bashiri Dezfouli, Ali
• Salar‐Amoli, Jamileh
• Pourfathollah, Ali Akbar
• Yazdi, Mina
• Nikougoftar‐Zarif, Mahin
• Khosravi, Mohammad
• Hassan, Jalal

Titel

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

Ist Teil von

• Journal of cellular physiology, 2020-03, Vol.235 (3), p.2336-2349

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2020

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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‐κB 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 β‐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 β‐galactosidase activity. Interestingly, the enhanced level of NF‐κB 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 β‐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. In our study, the changing pattern of indicators of cell senescence was investigated after exposure to doxorubicin in mesenchymal stem cells (MSCs) derived from mouse bone marrow with 1, 8, and 16 months of age. Furthermore, the differences in the drug absorption rate between the mentioned age group MSCs were evaluated by high‐performance liquid chromatography technique. The highest and lowest doxorubicin‐induced sensitivity to telomere shortening attributed to 1‐ and 8‐month‐old MSCs, respectively.